Nm23 mRNA Research Articles

Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer.

Correlation of sex determining region Y-box (SOX)9 and NM23 genes with the incidence and prognosis of prostate cancer (PC) was investigated. SOX9-small interfering ribonucleic acid (siRNA) and NM23-siRNA were constructed and transfected into PC-3 cells. The expression levels of SOX9 and NM23 messenger RNAs (mRNAs) and proteins in PC-3 cells were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. MTT assay was adopted to examine the proliferation ability of the transfected cells, and Transwell assay was applied to detect the migration ability of the transfected cells. Sixty-three patients with PC and 56 patients with benign prostatic hyperplasia who were treated in Huadu District People's Hospital were enrolled. Correlation analyses were conducted for the relative expression levels of SOX9 and NM23 and the Gleason grade; and the survival curves of the patient SOX9/NM23 (S/N) Cq values were plotted. The proliferation and migration abilities of PC-3 cells were remarkably reduced after low expression of SOX9 (P<0.01), while those of PC-3 cells were significantly improved after low expression of NM23 (P<0.01). Compared with that in tissues of PC patients, the relative expression of SOX9 mRNA in patients with benign prostatic hyperplasia was obviously decreased (P<0.01), while that of NM23 mRNA was significantly elevated (P<0.01). The larger the S/N was, the shorter the patient's survival time would be (P<0.05). The low expression of SOX9 gene can significantly reduce the proliferation and migration abilities of PC cells, which is negatively associated with the incidence and prognosis of patients. The low expression of NM23 gene can markedly enhance the proliferation and migration abilities of PC cells, and it is positively related to the incidence and prognosis of patients.

Molecular cloning, characterization and expression analysis of two apoptosis genes, caspase and nm23, involved in the antibacterial response in Chinese mitten crab, Eriocheir sinensis

Apoptosis is a central regulatory feature of the immune system, and the most common form of death among immunological cells. However, the function of apoptosis, within the innate immune system of invertebrates, remains largely unknown. For this reason, we investigated the immune functionality of two apoptosis genes, caspase and nm23, in the Chinese mitten crab ( Eriocheir sinensis), which is a commercially important and disease vulnerable aquaculture species. The entire length caspase and nm23 cDNA genes were cloned using PCR, based on an initial expressed sequence tag (EST) isolated from a hepatopancreatic cDNA library. The caspase cDNA contained an 1119 bp open reading frame that encoded a putative 372 amino acid protein, while nm23 cDNA contained a 456 bp open reading frame that encoded a putative 151 amino acid protein. Comparison, with other reported invertebrate and vertebrate sequences, revealed the presence of conserved enzyme active sites that were common among caspase and nm23 superfamilies. In brief, caspase and nm23 mRNA expression in E. sinensis were (a) both detected in all tissues, including the hemocytes, heart, hepatopancreas, gill, stomach, muscle, intestine, brain and eyestalk, and (b) responsive in hemocytes, gill and hepatopancreas to a Vibrio anguillarum immuno-challenge all appeared sharp increase. Collectively, the data presented here demonstrate the successful isolation of caspase and nm23 apoptosis genes from the Chinese mitten crab, and their role in the innate immune system of an invertebrate.

Proteomics of AML1/ETO Target Proteins: AML1–ETO Targets a C/EBP–NM23 Pathway

Abstract Introduction The rational design of targeted therapies for acute myeloid leukemia (AML) requires the discovery of novel protein pathways in the systems biology of a specific AML subtype. We have shown that in the AML subtype with translocation t(8;21), the leukemic fusion protein AML1–ETO inhibits the function of transcription factors PU.1 and C/EBPα via direct protein–protein interaction. In addition, recently using proteomics, we have also shown that the AML subtypes differ in their proteome, interactome, and post-translational modifications. Methods We, therefore, hypothesized that the systematic identification of target proteins of AML1–ETO on a global proteome-wide level will lead to novel insights into the systems biology of t(8;21) AML on a post-genomic functional level. Thus, 6 h after inducible expression of AML1–ETO, protein expression changes were identified by two-dimensional gel electrophoresis and subsequent mass spectrometry analysis. Results Twenty-eight target proteins of AML1–ETO including prohibitin, NM23, HSP27, and Annexin1 were identified by MALDI-TOF mass spectrometry. AML1–ETO upregulated the differentiation inhibitory factor NM23 protein expression after 6 h, and the NM23 mRNA expression was also elevated in t(8;21) AML patient samples in comparison with normal bone marrow. AML1–ETO inhibited the ability of C/EBP transcription factors to downregulate the NM23 promoter. These data suggest a model in which AML1–ETO inhibits the C/EBP-induced downregulation of the NM23 promoter and thereby increases the protein level of differentiation inhibitory factor NM23. Conclusions Proteomic pathway discovery can identify novel functional pathways in AML, such as the AML1–ETO–C/EBP–NM23 pathway, as the main step towards a systems biology and therapy of AML.

Expression patterns of nm23 genes during mouse organogenesis

Nucleoside di-phosphate kinase enzyme (NDPK) isoforms, encoded by the nm23 family of genes, may be involved in various cellular differentiation and proliferation processes. We have therefore analyzed the expression of nm23-M1, -M2, -M3, and -M4 during embryonic mouse development. In situ hybridization data has revealed the differential expression of nm23 mRNA during organogenesis. Whereas nm23-M1 and -M3 are preferentially expressed in the nervous and sensory systems, nm23-M2 mRNA is found ubiquitously. Irrespective of the developmental state studied, nm23-M4 mRNA is only expressed at low levels in a few embryonic organs. In the cerebellum and cerebral cortex, nm23-M1, -M2, and -M3 are present in the neuronal differentiation layer, whereas nm23-M4 mRNA is distributed in the proliferating layer. Thus, nm23 mRNA is differentially expressed, and the diverse NDPK isoforms are sequentially involved in various developmental processes.

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6, and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma, intraductal carcinoma of breast, and lung cancer. Using tissue microarray by immuhistochemical (IHC) staining and in situ hybridization (ISH), we examined the expression levels of nm23 mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6 in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer. The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P>0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P>0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P<0.01; r = -4.93, P<0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P<0.05; P<0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P<0.01; r = 5.04, P<0.01). CD44s and CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P<0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (c2 = 5.68, P<0.05). The expressional level of nm23 mRNA was closely related to the degree of cell differentiation (P<0.05) and lymph node metastasis (P<0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P>0.05). Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.

Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China

E-cadherin, a calcium-dependent cell-cell adhesion molecule, functions as maintenance of epithelial integrity. nm23, encoded by non-metastatic 23 gene, plays a key role in differentiation of many kinds of epithelium. Loss or dysfunction of E-cadherin and nm23 was frequently identified in many types of human cancers and is considered to correlate with invasive/metastatic phenotype. We previously reported that defective expression of E-cadherin might play a role in the development of the malignant phenotype in non-small cell lung cancer (NSCLC) [Q.Y. Fei, H.T. Zhang, X.F. Chen, et al., Defected expression of Ecadherin in non-small cell lung cancer, Lung Cancer 37 (2002) 147-152]. In an attempt to evaluate the significance of E-cadherin and nm23 in human non-small cell lung cancer, we performed mRNA expression and genetic structure analyses of the E-cadherin and nm23 genes in 54 NSCLCs and 46 normal lung tissues. The mRNA expression was determined by semi-quantitative RT-PCR, and genetic structure was examined through PCR-SSCP followed by sequencing. Although no mutation of the E-cadherin and nm23 genes was detected, the results obtained in the present study showed that reduction of E-cadherin and nm23 mRNA expression remarkably correlated with low histological differentiation, increasing stage as well as lymph node metastases (P<0.05). These data provide us with support for the idea that dysfunction of E-cadherin and nm23 has a role in progression of NSCLC and that the examination of E-cadherin and nm23 expression can provide experimental evidence for clinical treatment.

Related Study on the Nm23-H1 Gene Expression in the Model of Ovarian Carcinoma Cell Lines with High Frequent Metastasis

Objective: To select the ovarian carcinoma cell lines with high frequent metastasis and study the association between nm23-H1 gene expression and metastasis of ovarian carcinoma. Methods: Each ovarian cancer cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting lung tumor foci at different time points. The metastatic tumors were cultured in vitro, then substrain was established and transplanted subcutaneously three times. The RNA level of nm23 in 8 human ovarian cancer cell lines were examined by northern-blot. Results: Of the 8 human ovarian cancer cell lines, 4 had high requent metastatic potentiality. The expression of nm23 RNA in human ovarian cancer cells was inversely related to metastatic behavior in the experimental animals (r=0.96, P=0.0001). Conclusion: The difference of the tendency of metastasis which was determined by genetic and molecular levels was significant among different type of cell lines and subtypes. The expression of nm23 mRNA in human ovarian carcinomas was correlated closely with the reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator for ovarian cancer.

Taxol inhibits melanoma metastases through apoptosis induction, angiogenesis inhibition, and restoration of E-cadherin and nm23 expression.

An in vivo melanoma spontaneous metastases model was adopted to study the molecular mechanisms of the anti-metastatic effect of Taxol. The morphology of melanoma cells in the melanoma tissue lesions was examined by hematoxylin/eosin (H&E) staining and electron microscopy. The in situ programmed cell death was tested by TUNEL analysis. Vascular endothelial growth factor (VEGF) and E-cadherin expression were detected by immunohistochemistry. The metastases suppressor gene nm23 mRNA expression level was analyzed by in situ hybridization. The results showed that i.p. injection of Taxol at 5 mg/kg per day for three weeks significantly inhibited metastases formation in the pulmonary of mice. Taxol induced melanogenesis and apoptosis in the melanoma cells, inhibited angiogenesis in melanoma tissue lesions, and reduced the expression of VEGF. Conversely, Taxol increased the expression of E-cadherin and nm23. In conclusion, administration of Taxol in the early stage of melanoma metastases can significantly inhibit melanoma metastases. This effect was possibly related to apoptosis induction, tumor angiogenesis inhibition, and restoration of the metastasis suppression ability.

Serum nm23-H1 Protein as a Prognostic Factor in Hematological Malignancies

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-H1 levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), serum nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H1protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.

Correlation of MTS1/p16 and nm23 mRNA expression with survival in patients with peripheral synovial sarcoma

Background and Objectives Tumor supressor gene MTS1/p16 (cyclin-dependent kinase-4 inhibitor) and a putative tumor metastasis supressor gene nm23 (nucleoside diphosphate A kinase) have been identified in a variety of human tumors but have not been well studied in mesenchymal neoplasms. Methods Expression of nm23 and MTS1 mRNA was determined by quantitative analysis from paraffin-embedded tumor tissue. The series comprised 31 patients with localized primary synovial sarcoma of soft tissues who were followed for a median of 83 months. Results Neither MTS1 nor nm23 expression levels correlated with the patient's age or sex, tumor type, depth, size, mitotic rate, or extent of tumor necrosis. In addition, there was no correlation between MTS1 and nm23 levels. Patients' survival was not related to sex, age, tumor type, location, mitotic rate, or MTS1 mRNA level. The only factors that correlated with poor survival in multivariate analysis were the presence of extensive tumor necrosis (> 15%) and higher levels of nm23 mRNA. Conclusions Our results suggest that increased expression level of nm23 mRNA may be implicated in the mechanism of tumor progression and is associated with poor survival in patients with synovial sarcoma. J. Surg. Oncol. 2001;76:83–88. © 2001 Wiley-Liss, Inc.

Correlation of MTS1/p16 and nm23 mRNA expression with survival in patients with peripheral synovial sarcoma.

Tumor suppressor gene MTS1/p16 (cyclin-dependent kinase-4 inhibitor) and a putative tumor metastasis suppressor gene nm23 (nucleoside diphosphate A kinase) have been identified in a variety of human tumors but have not been well studied in mesenchymal neoplasms. Expression of nm23 and MTS1 mRNA was determined by quantitative analysis from paraffin-embedded tumor tissue. The series comprised 31 patients with localized primary synovial sarcoma of soft tissues who were followed for a median of 83 months. Neither MTS1 nor nm23 expression levels correlated with the patient's age or sex, tumor type, depth, size, mitotic rate, or extent of tumor necrosis. In addition, there was no correlation between MTS1 and nm23 levels. Patients' survival was not related to sex, age, tumor type, location, mitotic rate, or MTS1 mRNA level. The only factors that correlated with poor survival in multivariate analysis were the presence of extensive tumor necrosis (> 15%) and higher levels of nm23 mRNA. Our results suggest that increased expression level of nm23 mRNA may be implicated in the mechanism of tumor progression and is associated with poor survival in patients with synovial sarcoma.

Identification by Array Screening of Altered nm23-M2/PuF mRNA Expression in Mouse Retinal Degeneration

In the rd/rd mouse model of inherited retinal degeneration, the majority of photoreceptors die apoptotically between postnatal age (P)10 and 20 days, during which period the inner retina appears morphologically unaffected. To examine mRNA changes associated with the degeneration, we performed differential screening of 588 arrayed murine cDNAs using probes reverse-transcribed from P8 predegenerative and control mouse retinal RNAs. We detected altered expression of the gene encoding nm23-M2, a member of the family of nucleoside diphosphate kinases implicated in diverse processes including metastasis suppression and transcriptional regulation. Retinal nm23 mRNA levels increased during degeneration while control levels decreased over age-matched time-points. In situ hybridization showed the high level of expression at P20 in rd/rd was concentrated in the retinal ganglion cells. Previous studies have indicated upregulation of the stress-response related gene αB-crystallin in the rd/rd inner retina, and increased nm23 levels may be a component of this response to photoreceptor loss and altered retinal architecture.

Northern blot analysis of nm23 gene expression in human lung cancer

To investigate the role of nm23 gene expression in lung cancer. Forty human lung cancer tissues and 19 non-cancerous pulmonary tissues were studied for their nm23-H1 and nm23-H2 mRNA expression with nonradioactive Northern blot hybridization. Correlation of nm23 mRNA expression with clinical features of lung cancer was analyzed. The mRNA expression of nm23-H2 gene in poorly differentiated squamous-cell carcinoma was significantly decreased compared to that in moderately differentiated squamous-cell carcinoma. The mRNA expression of nm23-H1 and nm23-H2 genes in small cell lung cancer was decreased compared to that in squamous-cell carcinoma. No significant difference in nm23 mRNA expression was observed in lung cancers with and without lymph node metastasis, nor was there significant difference in patients with lung cancers in different stages. The mRNA expression of nm23 gene is correlated with the degree of differentiation of lung cancer, but there is no evidence of metastasis suppression effect by nm23 gene.

Expression of the tumor metastatic suppressor gene in mouse melanoma model: inverse association to metastatic potential.

Data obtained in experimental cutaneous melanomas have suggested that the nm23 gene may function as a metastasis suppressor gene. The nm23 level in 8 human cutaneous melanoma cell lines and 2 murine melanoma cell lines were examined. Each melanoma cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting lung tumor foci and by determining host survival time. It was found that expression of nm23 mRNA in human melanomas is correlated closely with reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator of malignancy and survival in patients with melanomas.

ALTERATIONS OF THE METASTASIS SUPPRESSOR GENE nm23 AND THE PROTO-ONCOGENE c-myc IN HUMAN TESTICULAR GERM CELL TUMORS

The putative metastasis suppressor genes nm23-H1, nm23-H2 and the c-myc proto-oncogene were investigated in testicular germ cell tumors (GCTs) using Southern and Northern blotting as well as semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analysis. When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases. A 2 to 7 fold nm23 mRNA overexpression was found in 22/34 (64.7%) tumors examined. RT-PCR revealed that this phenomenon is mainly a consequence of nm23-H2 overexpression. Overexpression of both the H1 and the H2 gene was predominantly found in the seminoma subtype and was not associated with tumor stage. Only 1/25 tumors, a seminoma with distant metastases, had a point mutation in the coding region of the nm23-H2 gene as demonstrated by SSCP analysis. None of the 8 seminomas and only 1/13 non-seminomas had c-myc overexpression. No abnormalities of the c-myc gene could be detected on the DNA level. Despite the fact that in previous investigations nm23-H2 was demonstrated to be a putative transcription factor for c-myc, no coexpression of c-myc and nm23-H2 was found by quantitative RT-PCR in this study.

Expression of NM23 in human melanoma progression and metastasis.

NM23 is a putative metastasis-suppressor gene for some human cancers. Here we have studied NM23 expression during melanoma progression using Northern blotting and immunocytochemistry. There was no significant difference in the average amounts of NM23 mRNA between cell lines derived from metastatic and primary melanomas. The level of NM23 mRNA was also determined for three pairs of poorly metastatic parental (P) and their highly metastatic variant (M) cell lines; the ratios for M/P were 1.2, 0.98 and 0.80. Next we used immunocytochemistry to study NM23 protein in normal skin, benign naevi and primary and metastatic melanomas. Melanocytes in all normal skin and benign samples were positive for NM23; however most primary melanomas (7/11) were not stained by the antibody. All metastatic melanoma samples (5/5) were positively stained. Findings were similar with an antiserum reactive with both forms of NM23 (H1 and H2), and with an antibody specific for NM23-H1. No relationship was apparent between NM23 immunoreactivity in primary tumours and their aggressiveness or prognosis. Hence, in contrast to the situation described for murine melanoma, the amount of NM23 mRNA or protein in human melanoma did not correlate inversely with metastasis.

MRNA levels of nm23 in murine ascites hepatoma (H22) clones with different lymphatic metastatic potential.

Levels of expression of the nm23 gene inversely correlated with metastatic potential in several rodent tumor model systems and human breast carcinoma. In the present study, we examined nm23 mRNA levels in two murine ascites hepatoma models (H22-16A3-F and H22-A2-P) with different metastatic potentials. Metastatic H22-16A3-F (80% metastatic rate) and non-metastatic H22-A2-P clones were both derived from murine ascites hepatoma (H22). We found that a 0.8-kb nm23 transcript was expressed in both cell clones. The nm23 gene was expressed at a higher level in non-metastatic H22-A2-P: approximately 8.6-fold higher than in metastatic H22-16A3-F. The present data suggest that the expression of nm23 mRNA might be associated with metastasis of murine ascites hepatoma (H22), though heterogeneity of nm23 steady-state expression levels among the H22 clones remains to be investigated.

Coexpression Pattern of C-MYC Associated Genes in a Small Cell Lung Cancer Cell Line with High Steady State C-MYC Transcription

The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxil was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation. c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.

Expression of NM23 in Cell Lines Derived from Patients with Metastatic Renal Cell Carcinoma

Reduced expression of nm23 has been associated with increased metastases and decreased survival in a variety of malignancies. In the present study, the expression of nm23 was examined by Northern and Western blot analyses in a series of cell lines derive from patients with metastatic renal cell carcinoma. Two of twelve (17 percent) informative cell lines derived from 9 patients had loss of heterozygosity at Nm23-H1. Twenty-two renal cancer cell lines derived from primary tumors, 5 cell lines derived from metastatic tumors and 4 short-term cultures of normal proximal renal tubular cells all expressed Nm23 mRNA in varying amounts. On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines. Twenty-eight cell lines derived from renal primary tumors and 8 cell lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins. High or low relative expression of nm23 at the mRNA or protein level did not correlate with survival. The absence of any anomalous pattern of expression of the nm23 genes and the lack of correlation of expression with survival suggests that nm23 does not play a central role in the progression of this tumor type.

Effects of 5α-Dihydrotestosterone (DHT) on the Transcription of nm23 and c-myc Genes in Human Prostatic LNCaP Cells

Proliferation of the androgen-dependent human prostate LNCaP cells was increased by the androgen DHT. Changes in the steady state level of the nm23 and c-myc mRNA in LNCaP cells, with or without 10 nM DHT, showed the nm23 mRNA to change rapidly, beginning to rise after 2 h and reaching its peak by 4 h of DHT treatment. In contrast, increases in the c-myc gene only became apparent after 4 h of treatment. Maximal increase of nm23 mRNA was observed at 10−9 M DHT. The basal expression of c-myc and nm23 mRNAs was between 30-70% lower in the LNCaP cells, as compared with the androgen-independent PC-3 and JCA-1 human prostatic human carcinoma cells. Thus nm23 may be classified as a member of the early androgen-responsive genes.