Hormone Deprivation Research Articles

Aging induced additional impairment in cardiovascular control in ovariectomized rats

The objective was to investigate the effects of aging on cardiovascular parameters in females rats submitted to ovarian hormones deprivation. Female Wistar rats were divided into 4 groups (n=8 each group): young adult (2–3 mo, YA), aged (18 mo, AG), young adult ovariectomized (YA‐OVX) and aged ovariectomized (AG‐OVX). Arterial pressure (AP) and heart rate (HR) signals were directly recorded in conscious rats. The baroreflex sensitivity (BRS) was evaluated by tachycardic (TR) and bradycardic (BR) responses. The ovariectomy, associated or not with aging, induced increase in AP values (YA‐OVX: 124±1.35 and AG‐OVX: 136±7.06 vs. YA: 112±2.56 mmHg). There was an additional AP increase in AG‐OVX in relation to YA‐OVX and AG rats (120±2.6 mmHg). The HR was enhanced in AG, YA‐OVX, AG‐OVX when compared with YA group. The BR and TR were impaired in AG (0.83±0.06 and 1.50±0.28 bpm/mmHg) as compared to YA group (1.27±0.08 and −3.70±0.30 bpm/mmHg). Ovariectomy (YA‐OVX: 1.09±0.08 and 2.11±0.21 and AG‐OVX: 0.54±0.05 and −0.88±0.33 bpm/mmHg) decreased both BR and TR in relation to YA and AG groups. Furthermore, BRS was additionally reduced in AG‐OVX as compared to YA‐OVX rats. These results demonstrated that the ovarian hormone deprivation impact on arterial pressure and BRS is aged dependent.

Donepezil and tacrine differentially interact with estradiol in female rats responding under a multiple schedule of repeated acquisition and performance

In females, ovarian hormones can facilitate learning and memory processes but such beneficial effects are often lost or diminished following long‐term hormone deprivation. Because the absence of estradiol disrupts learning and memory presumably by reducing the activity of the cholinergic system, acetylcholinesterase (AchE) inhibitors may reverse this disruption by enhancing the functional status of the cholinergic system. This study investigated the interactive effects of estrogen and two AchE inhibitors, donepezil (0.56–5.6 mg/kg) and tacrine (0.56–10 mg/kg), in subjects responding under a multiple schedule of repeated acquisition and performance of response chains. Dose‐effect curves were determined in female rats that were gonadally intact, ovariectomized, or ovariectomized with estradiol replacement. In all three groups, both drugs produced dose‐dependent rate‐decreasing and error‐increasing effects in the acquisition and performance components. However, OVX females were less sensitive to the error‐increasing effects of donepezil in the acquisition component and the error‐increasing effects of tacrine in the performance component. These data extend the current knowledge regarding the effects of estrogen on nonspatial learning and memory tasks, and help determine if estradiol's capacity for mediating responding on such tasks is related to its ability to affect cholinergic neurotransmission. Supported by DA019625 and Contract NSF(2010)‐PFUND‐198 Board of Regents of Louisiana

Calorie restriction prevents the development of insulin resistance and impaired insulin signaling in skeletal muscle of ovariectomized rats

Insulin resistance of skeletal muscle glucose transport due to prolonged loss of ovarian function in ovariectomized (OVX) rats is accompanied by other features of the metabolic syndrome and may be confounded by increased calorie consumption. In this study, we investigated the role of calorie consumption in the development of insulin resistance in OVX rats. In addition, we examined the cellular mechanisms underlying skeletal muscle insulin resistance in OVX rats. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (SHAM). OVX rats either had free access to food, pair feeding (PF) with SHAM or received a 35% reduction in food intake (calorie restriction; CR) for 12weeks. Compared with SHAM, ovariectomy induced skeletal muscle insulin resistance, which was associated with decreases (32–70%) in tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), IRS-1 associated p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase), and Akt Ser473 phosphorylation whereas insulin-stimulated phosphorylation of IRS-1 Ser307, SAPK/JNK Thr183/Tyr185, and p38 mitogen-activated protein kinase (MAPK) Thr180/Tyr182 was increased (24–62%). PF improved the serum lipid profile but did not restore insulin-stimulated glucose transport, indicating that insulin resistance in OVX rats is a consequence of ovarian hormone deprivation. In contrast, impaired insulin sensitivity and defective insulin signaling were not observed in the skeletal muscle of OVX+CR rats. Therefore, we provide evidence for the first time that CR effectively prevents the development of insulin resistance and impaired insulin signaling in the skeletal muscle of OVX rats.

Abstract C38: Whole-genome sequencing of paired androgen-dependent and -independent prostate cancer cell lines: Potential role of novel targets in PI3K and Notch signaling pathways in resistance to hormonal therapy

Abstract The growth of the majority of prostate tumors is driven by androgens signaling through the androgen receptor. Most patients initially respond to androgen deprivation therapies such as LHRH analogues and anti-androgens like bicalutamide, but after a varying duration of treatment, patients generally develop resistance to these therapies and their tumor progresses to an androgen independent state. Molecular mechanisms that drive androgen independent disease include mutation and amplification of androgen receptor (AR), androgen-independent activation of AR, and AR-independent mechanisms. The aim of this project was to sequence the entire genome of pairs of cell lines, modeling the progression to androgen independent disease, to increase our understanding of these mechanisms and identify new therapeutic targets. Four ‘parental’ prostate cancer cell lines, all of which are sensitive to hormone deprivation, and an androgen independent derivative of each line, derived either by culturing in bicalutamide or growing in the absence of androgens, were subjected to whole genome sequencing. Genomic variants present in the androgen independent but not the parental lines, presumed to be acquired during the progression to androgen independence, were then identified. To find any commonality between the four different pairings, the derived variants were then mapped to functional biological pathways and their likely impact on protein function predicted. Interestingly, derived mutations in the PI3K and Notch signaling pathways were identified in multiple cell lines. In addition to the analysis of derived mutations, baseline characterization of genomic rearrangements and copy number changes in cell lines highlighted variability in the patterns and prevalence of these events as well as uncovering aberrations in genes known to impact prostate cancer development (PTEN, AR, TMPRSS2 rearrangement). This extensive genome sequencing effort has yielded a deeper understanding of potential pathways and molecular events that occur during the acquisition of resistance to anti-androgen therapy, using in vitro models of prostate cancer. These candidates now require validation in tissue samples from prostate cancer patients and functional assays. Citation Format: Gillian L. Dalgliesh, Joanne L. Hartley, Cary H. O'Donnell, James R. Bradford, Iain McKendrick, Barry R. Davies. Whole-genome sequencing of paired androgen-dependent and -independent prostate cancer cell lines: Potential role of novel targets in PI3K and Notch signaling pathways in resistance to hormonal therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C38.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer

Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC), which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17). This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.

Musculoskeletal events associated with the management of endocrine-responsive breast cancer

Musculoskeletal symptoms have been reported in patients treated with third generation aromatase inhibitors (AIs) and with blockers of hypothalamic–pituitary gonadal axis. AIs act by suppressing postmenopausal estrogen biosynthesis through inhibition of the enzyme aromatase, which is responsible for the conversion of androgens to estrogens in many tissues. Maximal estrogen and/or androgen deprivation is beneficial for cancer growth suppression but could be associated with side effects such as accelerated bone loss and osteoporotic fractures which are extensively reported. Musculoskeletal events, another group of adverse events, have been studied to a lesser extent and are usually commonly reported as arthralgia and myalgia. Furthermore, the pathogenesis and anatomical findings of musculoskeletal symptoms have not been adequately elucidated. In this communication, we review recent information related to musculoskeletal symptoms in breast cancer and speculate on possible explanations for musculoskeletal pain related to hormone deprivation. We outline treatment options for control of arthralgia and myalgia due to hormonal therapy. More knowledge about the etiology and management of musculoskeletal adverse effects breast cancer during endocrine therapy is needed because discontinuation of the treatment due to intolerant symptomatology may result in disruption of the treatment schedule.

Visuospatial Associative Memory and Hippocampal Functioning in Congenital Hypothyroidism

Congenital hypothyroidism is a pediatric endocrine disorder caused by insufficient endogenous thyroid hormone production. Children with congenital hypothyroidism have difficulties with episodic memory and abnormalities in hippocampal structure, suggesting deficient hippocampal functioning. To assess hippocampal activation in adolescents with congenital hypothyroidism (N = 14; age range, 11.5-14.7 years) compared with controls (N = 15; age range, 11.2-15.5 years), a functional magnetic resonance imaging visuospatial memory task was used. In this task, participants had to decide if object pairings were novel or were previously studied or if object pairs were in the same location as they were at study or had switched locations. Despite no group differences in task performance, adolescents with congenital hypothyroidism showed both increased magnitude of hippocampal activation relative to controls and bilateral hippocampal activation when only the left was observed in controls. Furthermore, the increased activation in the congenital hypothyroidism group was correlated with the severity of the hypothyroidism experienced early in life. These results suggest that perinatal deprivation of thyroid hormone has longstanding effects on hippocampal function and may account for memory problems experienced by adolescents with congenital hypothyroidism.

Can erectile function be predicted after prostate cancer treatment?

Can erectile function be predicted after prostate cancer treatment?

Selective estrogen receptor modulators regulate dendritic spine plasticity in the hippocampus of male rats.

Some selective estrogen receptor modulators, such as raloxifene and tamoxifen, are neuroprotective and reduce brain inflammation in several experimental models of neurodegeneration. In addition, raloxifene and tamoxifen counteract cognitive deficits caused by gonadal hormone deprivation in male rats. In this study, we have explored whether raloxifene and tamoxifen may regulate the number and geometry of dendritic spines in CA1 pyramidal neurons of the rat hippocampus. Young adult male rats were injected with raloxifene (1 mg/kg), tamoxifen (1 mg/kg), or vehicle and killed 24 h after the injection. Animals treated with raloxifene or tamoxifen showed an increased numerical density of dendritic spines in CA1 pyramidal neurons compared to animals treated with vehicle. Raloxifene and tamoxifen had also specific effects in the morphology of spines. These findings suggest that raloxifene and tamoxifen may influence the processing of information by hippocampal pyramidal neurons by affecting the number and shape of dendritic spines.

A Kinome-Wide Screen Identifies the Insulin/IGF-I Receptor Pathway as a Mechanism of Escape from Hormone Dependence in Breast Cancer

Estrogen receptor α (ER)-positive breast cancers adapt to hormone deprivation and become resistant to antiestrogens. In this study, we sought to identify kinases essential for growth of ER(+) breast cancer cells resistant to long-term estrogen deprivation (LTED). A kinome-wide siRNA screen showed that the insulin receptor (InsR) is required for growth of MCF-7/LTED cells. Knockdown of InsR and/or insulin-like growth factor-I receptor (IGF-IR) inhibited growth of 3 of 4 LTED cell lines. Inhibition of InsR and IGF-IR with the dual tyrosine kinase inhibitor OSI-906 prevented the emergence of hormone-independent cells and tumors in vivo, inhibited parental and LTED cell growth and PI3K/AKT signaling, and suppressed growth of established MCF-7 xenografts in ovariectomized mice, whereas treatment with the neutralizing IGF-IR monoclonal antibody MAB391 was ineffective. Combined treatment with OSI-906 and the ER downregulator fulvestrant more effectively suppressed hormone-independent tumor growth than either drug alone. Finally, an insulin/IGF-I gene expression signature predicted recurrence-free survival in patients with ER(+) breast cancer treated with the antiestrogen tamoxifen. We conclude that therapeutic targeting of both InsR and IGF-IR should be more effective than targeting IGF-IR alone in abrogating resistance to endocrine therapy in breast cancer.

Intraoperative finding of gross lymph node metastasis during robot-assisted prostatectomy

Discovery of macroscopically positive lymph nodes (LN) during radical prostatectomy for clinically localized prostate cancer (PCa) is a rare event. We describe our experience of intraoperative finding of grossly positive LN during radical prostatectomy and evaluate outcomes and predictors. A total of 4,480 patients underwent robot-assisted radical prostatectomy (RARP) for clinically localized PCa from 2001 to 2010, and pelvic LN dissection was performed in 4,090 of these patients (91.3%). Patients with macroscopically positive LN discovered and confirmed intraoperatively were assessed, as was surgical decision (abort versus continue RARP). Patients with macroscopic LN-positive disease were also evaluated and oncologic outcomes were compared with patients with microscopic LN-positive disease on final pathology. LN-positive disease was found at final pathology in 87 patients (2.1%), of whom 13 (14.9%) had grossly abnormal LN confirmed intraoperatively by frozen section. RARP was aborted in nine cases and completed in four patients. All patients received adjuvant therapy with hormonal deprivation and/or radiation. Two patients in the aborted RARP subset died of PCa. All patients who underwent completion RARP are still alive at a mean follow-up of 57.2months with one patient still alive at 95months. Patients with macroscopically positive LN had a higher median preoperative prostate serum antigen (PSA) (17.2 vs. 6.7 μg/L, P=0.002) and were more likely have biopsy perineural invasion (77.8 vs. 32.4%, P=0.012). Intraoperative findings of macroscopically positive LN during RARP is a rare event that may occur in high-risk patients, particularly in those with a high PSA and biopsy perineural invasion. Long-term survival is possible after completion RARP.

Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomized rats

We hypothesize that beneficial effects of estradiol on cognitive performance diminish with age and time following menopause due to a progressive decline in basal forebrain cholinergic function. This study tested whether galanthamine, a cholinesterase inhibitor used to treat memory impairment associated with Alzheimer's disease, could enhance or restore estradiol effects on cognitive performance in aged rats that had been ovariectomized in middle-age. Rats were ovariectomized at 16–17months of age. At 21–22months of age rats began receiving daily injections of galanthamine (5mg/day) or vehicle. After one week, half of each group also received 17ß-estradiol administered subcutaneously. Rats were then trained on a delayed matching to position (DMP) T-maze task, followed by an operant stimulus discrimination/reversal learning task. Treatment with galanthamine+estradiol significantly enhanced the rate of DMP acquisition and improved short-term delay-dependent spatial memory performance. Treatment with galanthamine or estradiol alone was without significant effect. Effects were task-specific in that galanthamine+estradiol treatment did not significantly improve performance on the stimulus discrimination/reversal learning task. In fact, estradiol was associated with a significant increase in incorrect responses on this task after reversal of the stimulus contingency. In addition, treatments did not significantly affect hippocampal choline acetyltransferase activity or acetylcholine release. This may be an effect of age, or possibly is related to compensatory changes associated with long-term cholinesterase inhibitor treatment. The data suggest that treating with a cholinesterase inhibitor can enhance the effects of estradiol on acquisition of a DMP task by old rats following a long period of hormone deprivation. This could be of particular benefit to older women who have not used hormone therapy for many years and are beginning to show signs of mild cognitive impairment. Potential mechanisms for these effects are discussed.

Aktuelle Therapie des fortgeschrittenen Prostatakarzinoms

Despite the broad use of PSA-testing in western medicine, still an estimated 1/3 of carcinomas of the prostate (PC) are diagnosed in a locally advanced or metastatic stage. In the current treatment-algorithm for locally advanced PC, radical prostatectomy, external beam radiation therapy (with and without hormonal therapy) and primary androgen deprivation are available. In fact, in a majority of patients treatment of this tumor stage will be a multimodal approach, which has to be discussed individually. For metastatic PC hormonal deprivation therapy is still the gold standard. Beside LHRH-agonists, surgical castration and complete androgen deprivation today LHRH-antagonists represent the different therapeutic options in this tumor stage. Effects on natural course of this disease have to be balanced to the side effects of long-term therapy. Castration-resistant PC is not the object of this overview even though there are a variety of new medical interventions emerging for the treatment of this stage of PC.

A Comparative Analysis of Expression of Selected Genes During Induction of Differentiation in Neonatal Rats by Deprival of FSH or by Hyperthyroidism

The effect of Follicle Stimulating Hormone (FSH) deprivation, or hyperthyroidism, on the expression of selected genes in Sertoli cells of neonatal rats was compared, and significant differences were revealed. While hyperthyroidism resulted in both arrest of proliferation and expression of differentiation markers, FSH deprivation only resulted in arrest of proliferation, as assessed by a decrease in such proliferation markers as connective tissue growth factor (CTGF) and collagen 12A1 and the expression of differentiation markers, such as androgen binding protein, transferrin and clusterin. In Sertoli cells isolated from hyperthyroid rats, a decrease in the expression of FSH receptor was also observed. Microarray analysis of RNA from FSH-deprived or hyperthyroid neonatal rat Sertoli cells suggests that molecular events associated with arrest of proliferation by hyperthyroidism appear to be different from arrest of proliferation by FSH deprivation.

Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade

A single arm phase II trial of single-agent bortezomib (BZM) alone or combined with hormone blockade was conducted in patients with early PSA recurrence after definitive local therapy. The primary endpoint of this study was to determine the time to PSA relapse after BZM therapy alone or when BZM was combined with hormone blockade. The secondary endpoint was to determine the safety of combination therapy. Part A of the treatment schedule consisted of three cycles of BZM 1.3 mg/m2 IV given on days 1,4,8,11. If patients progressed on Part A, they were entered on Part B which consisted of a single dose of LH-RH antagonist, daily oral antiandrogen, and weekly BZM 1.3 mg/m2 for three out of four weeks for a total of three months. BZM treatment significantly decreased the slope of the log PSA (p=0.024) demonstrating that this agent alone was capable of slowing the rise of the PSA. Of eight patients treated with BZM alone five had stable disease, two progressed and 1 went off study secondary to toxicity. The major toxicity was neurotoxicity requiring discontinuation of therapy in three patients and treatment interruption in nine patients. Of those receiving Parts A and B or B only, there were 11 of 15 CRs with the average time to progression of 5.5 months. BZM treatment can change the slope of PSA rise and can be combined with hormone deprivation therapy without significant additional side effects; these agents are associated with a median time to CR of 42 days.

Raloxifene Reduces Blood Pressure in Hypertensive Animals after Ovarian Hormone Deprivation

Raloxifene is a selective oestrogen receptor modulator that has been approved for the prevention and treatment of osteoporosis in post-menopausal women. Studies have revealed several effects of raloxifene on the cardiovascular system, which might contribute to the blood pressure regulatory mechanisms, particularly in the systemic arterial hypertension. Therefore, the aim of this study was to investigate the effects of raloxifene on the blood pressure, renal excretion of water and Na(+) and plasma nitrite/nitrate levels in 2-kidney-1-clip (2K1C) hypertensive female rats. The groups were as follows: hypertensive (2K1C), hypertensive ovariectomized (2K1C + OVX) and hypertensive ovariectomized treated with raloxifene (2K1C + OVX + R). Seven days after the surgery that produced menopause, 2K1C hypertension was produced in anaesthetized animals. Seven days after the clip application, the rats were put into metabolic cages to allow for the measurement of water ingestion and diuresis, and raloxifene was administered (2 mg/kg/day i.p., for 7 more days). We found a large reduction (p < 0.01) in mean arterial pressure (197 ± 6 to 164 ± 2 mmHg), an increase in renal excretion of sodium and water (p < 0.05) and an increase in plasma levels of nitrite/nitrate in 2K1C + OVX + R animals, when compared with the 2K1C (23.4 ± 1 versus 14 ± 0.5 nmol/mL; p < 0.01, respectively). These findings suggest that raloxifene exerted its antihypertensive effect, at least in part, by improving the renal excretion of sodium and water.

Treatment of hot flushes in tumor patients with hormonal deprivation by magnesium – new aspects of a forgotten cation in oncology

Treatment of hot flushes in tumor patients with hormonal deprivation by magnesium – new aspects of a forgotten cation in oncology

Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid

Previously, we demonstrated that reproductive senescence was associated with mitochondrial deficits comparable to those of female triple-transgenic Alzheimer's mice (3xTgAD). Herein, we investigated the impact of chronic ovarian hormone deprivation and 17β-estradiol (E2) replacement on mitochondrial function in nontransgenic (nonTg) and 3xTgAD female mouse brain. Depletion of ovarian hormones by ovariectomy (OVX) in nontransgenic mice significantly decreased brain bioenergetics, and induced mitochondrial dysfunction and oxidative stress. In 3xTgAD mice, OVX significantly exacerbated mitochondrial dysfunction and induced mitochondrial β-amyloid and β-amyloid (Aβ)-binding-alcohol-dehydrogenase (ABAD) expression. Treatment with E2 at OVX prevented OVX-induced mitochondrial deficits, sustained mitochondrial bioenergetic function, decreased oxidative stress, and prevented mitochondrial β-amyloid and ABAD accumulation. In vitro, E2 increased maximal mitochondrial respiration in neurons and basal and maximal respiration in glia. Collectively, these data demonstrate that ovarian hormone loss induced a mitochondrial phenotype comparable to a transgenic female model of Alzheimer's disease (AD), which was prevented by E2. These findings provide a plausible mechanism for increased risk of Alzheimer's disease in premenopausally oophorectomized women while also suggesting a therapeutic strategy for prevention.

Abstract 495: Overexpression of the cold-inducible RNA binding protein RBM3 attenuates the stem cell-like features of PC-3 cells

Abstract Introduction: It has long been thought that the stem cell-like features of cancer cells contribute to their evolutionary capability to escape therapeutic strategies, such as chemotherapy, radiotherapy, or hormone deprivation in prostate cancer (PCa). At the same time, temperature is perhaps one of the most important elements of the environment. One of the most clinically relevant examples of the effect of temperature on stem-like cells is cryptorchidism, in which germ cells maintained at body temperature that is several degrees higher than in the scrotum do not function to form sperm. In contrast, these pluripotential cells have a high likelihood to develop cancer if they are not rescued by relocating them to the scrotum and therefore a lower environmental temperature, in very early childhood. RNA binding motif 3 (RBM3) belongs to a cold-inducible RNA binding protein family and has been shown to be highly expressed in normal testis tissue but is decreased in cryptorchid mouse. We previously reported that RBM3 was decreased by heat treatment in PCa cell lines. The goal of this study is to investigate the effect of RBM3 over-expression on stem cell-like features of PC-3 cells. Methods: RBM3 mRNA expression was detected by RT-PCR in fetal and adult human tissues, as well as in PCa samples. The normal prostate cell line, PrEc, was sorted with the stem cell surface marker CD133 using flow cytometry. PC-3 cells were transfected with pCMV6-RBM3-GFP vector. The soft agar clonogenic assay was performed with RBM3- or control vector-transfected cells. The expression of stem cell-related genes and miRNAs was determined using PCR array. Results: The RBM3 mRNA level is decreased in fetal tissues and CD133 (+) PrEc cells in comparison to adult tissues and CD133 (−) cells, respectively. Metastatic PCa expresses lower RBM3 mRNA than primary tumors. Moreover, RBM3 expression was decreased upon treatment of chemotherapy and maintained at a low level in the surviving clones after intensive chemo- or heat treatment in both PC-3 and DU-145 cells. PC-3 cells that over-express RBM3 demonstrated less heterogenic morphology than those with a control vector. Importantly, RBM3 over-expression greatly attenuates the anchorage-independent clonogenic ability of PC-3 cells. Additionally, a panel of genes and miRNAs that are involved in neural cell differentiation and self-renew are altered upon RBM3 expression. Conclusion: Taken together, these data suggest that lowering RBM3 may play an important role in maintaining the stem cell-like features of cancer cells during development and progression under environmental stress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 495. doi:10.1158/1538-7445.AM2011-495