Primary Prostate Tissue Research Articles

Stat3 activation in prostatic carcinomas.

Activated Stat3 is found in various types of immortal cell lines and cancers. We and others have previously demonstrated that Stat3 is constitutively activated in rat and human prostate cancer cell lines, and that Stat3 activation is involved in IL-6-mediated signaling transduction in prostate cancer cells. The aim of this study is to examine quantitative Stat3 activity in benign and malignant human prostate tissues and analyze the association between Stat3 activity levels and the clinical and pathologic parameters. Stat3 activity levels were analyzed in a total of 104 human primary prostate tissues using electromobility shift assay and immunohistochemical staining for phosphorylated Stat3. The tissue samples used were 42 prostate carcinomas, 42 matched normal prostate tissues from patients with prostatic adenocarcinoma (normal adjacent to tumor), and 20 normal prostate tissues from organ donors. Significantly higher levels of constitutive Stat3 activity were detected in both prostate carcinomas and the matched normal prostate tissues adjacent to tumors compared to the normal prostates from donors without prostate cancer. There was no significant difference of Stat3 activity in foci of tumor and normal prostate tissue adjacent to tumor. No correlation was seen between Stat3 activity and Gleason grade or serum PSA levels in samples from prostate carcinomas. These results indicate that Stat3 is constitutively activated in prostate cancer. The high level of Stat3 activity in both the prostate carcinomas and the normal prostate tissues adjacent to tumors suggests that Stat3 activation may occur before detectable histological alterations of the prostate.

Selective Activation Of Members Of The Signal Transducers And Activators Of Transcription Family In Prostate Carcinoma

Cytokines, hormones and growth factors use signal transducers and activators of transcription (STAT) signaling pathways to control various biological responses, including development, differentiation, cell proliferation and survival. Constitutive activation of STATs has been found in a wide variety of human tumors. In this study we examined the activity of STATs in primary human prostate tissues. STAT activity was determined in 104 human primary prostate tissues, including 42 tumors, 42 matched normal prostates adjacent to tumors and 20 normal prostates from donors without cancer by electromobility shift assay. Significant levels of activated Stat4 and Stat6 were detected in primary prostate tissues. However, little or no expression of active Stat1, Stat2 or Stat5 was detected in primary prostate tissues. Significantly higher levels of constitutive Stat6 activity were found in prostate carcinomas compared with levels in normal tissue adjacent to tumors and normal prostates from donors without prostate cancer. There was no significant difference in Stat6 activity in normal prostate tissues adjacent to tumors and normal prostates from donors without prostate cancer. The levels of Stat4 activity varied but failed to yield statistically significant differences among tumors, matched normal prostates adjacent to tumors and normal prostates from donors without cancer. We have previously shown that Stat3 is activated in prostate cancer. The results of the current study demonstrate that in addition to Stat3, Stat6 is selectively activated in prostate cancer.

Efficacy & stability of a PSA enhancer-promoter construct in prostate cell lines and primary prostate tissue

Efficacy & stability of a PSA enhancer-promoter construct in prostate cell lines and primary prostate tissue

Prognostic value of immunohistochemical expression of the c-erbB-2 oncoprotein in metastasic prostate cancer.

It is well established that the activation of proto-oncogenes could trigger uncontrolled cell growth and cancer development. Although this correlation has already been evidenced in several human tumors, no conclusive studies have related oncogene activation with the development of prostatic neoplasia. Nevertheless, some reports suggest that c-erbB-2, which is a prognostic marker in breast cancer, could be implicated in the development of prostatic adenocarcinoma. We have studied the expression of the c-erbB-2 oncoprotein in primary prostatic tissue in a series of 70 patients with metastasic disease, by means of immunohistochemistry. The NCL-B 11 anti-c-erbB-2 monoclonal antibody was used, and the immunoreactivity was quantified by image analysis. The overall rate of prostatic-tissue sections presenting positive c-erbB-2 immunostaining was 64.3%. No significant relation was observed between histological grade and c-erbB-2 over-expression or severity of the disease, based on the extent of metastases. The average specific survival in patients with c-erbB-2 over-expression was 33 months, while it was 54 in patients with c-erbB-2 negativity; p < 0. 034. These results, as well as the logistic-regression analysis, suggest that expression of c-erbB-2 oncoprotein would be considered as an independent prognostic factor of metastatic prostate cancer. Moreover, it could discriminate between the prognosis of patients with Gleason score 2 to 7 and those with score 8 to 10. Our results suggest that the expression of c-erbB-2 oncoprotein in primary prostatic tissue could have a prognostic value in patients with metastatic prostate cancer. Int. J. Cancer (Pred. Oncol.) 84:421-425, 1999.

Glutathione and glutathione S-transferase in benign and malignant prostate cell lines and prostate tissues

Metastatic prostate adenocarcinoma is unresponsive to alkylator chemotherapy with virtually no prolonged remissions. Glutathione (GSH) and glutathione S-transferase (GST) have been reported to play a role in tumor resistance to alkylator therapy; however, there are no baseline studies that have investigated and compared GSH and GST in human prostate cell lines and tissues. Thus, we determined the GSH content and GST activity in benign prostate, in primary and metastatic prostate adenocarcinoma tissues, in immortal adenocarcinoma cell lines, and in primary cell cultures derived from both benign prostate and primary prostatic carcinoma tissue. The GSH content was higher in the immortal cell lines than in the fresh tissues and primary cultures. Conversely, the GST activity was significantly higher in the tissues and primary cultures than in the cell lines. The GSH content and GST activity of the primary cultured prostatic cells were similar to those of the prostate tissues. The differences between the immortal prostate cancer cell lines and prostate tissue are of sufficient magnitude to suggest that in vitro results with cell lines may not extrapolate to prostate cancer in vivo. The GSH content and GST activity in a prostate specific antigen-secreting human prostate tumor xenograft, LuCaP23, maintained in nude mice were similar to those of human prostate tissue and primary cultures. Both the xenograft and primary cultures from patients with prostate cancer may be more appropriate models than established cell lines for investigating techniques to increase the effectiveness of alkylators in prostate cancer.

Analysis of hypoxia-associated gene expression in prostate cancer: lysyl oxidase and glucose transporter-1 expression correlate with Gleason score

Prostate cancer cells exist under hypoxic conditions. Hypoxia has a detrimental effect on the efficacy of treatment and final outcome in patients with prostate cancer. There have been a large number of endogenous markers of hypoxia described previously across a range of cancer types, both in vitro and in vivo. The aim of this study was to evaluate the expression of a range of hypoxia-associated genes within benign prostatic hypertrophy (BPH) and prostate cancer tissue. Messenger RNA was extracted from primary prostate tissue obtained from 67 men with benign prostatic hypertrophy or prostate cancer (Gleason score 5 to 10). Real-time polymerase chain reaction was performed to quantify the expression levels of 12 hypoxia-associated genes in these tissues. Expression of lysyl oxidase (LOX) and glucose transporter-1 (GLUT-1) genes were significantly higher in prostate cancer compared with BPH tissue (P<0.05) and correlated with Gleason score (LOX: R=0.297, P=0.015; GLUT-1: R=0.274, P=0.026). HIF-2alpha had a negative correlation with Gleason score (R= -0.309, P=0.012). The remaining hypoxia-associated genes did not show any specific pattern of expression in prostate tissue. Numerous molecules have been proposed as endogenous markers of hypoxia. The findings of this study illustrate that not all hypoxia-associated molecules are relevant to prostate cancer in vivo. However, LOX and GLUT-1 are candidate markers of hypoxia in prostate cancer and may prove useful in identifying patients with hypoxic prostate cancer. Not all hypoxia-associated molecules are relevant in prostate cancer in vivo.

Citrate alterations in primary and metastatic human prostatic adenocarcinomas: 1H magnetic resonance spectroscopy and biochemical study.

The objectives of this study were to quantitatively verify the low levels of citrate previously observed in primary human prostatic adenocarcinomas and to determine whether citrate was further reduced in metastatic prostatic cancer. This was accomplished by comparison of citrate concentrations of DU 145 xenografts (a poorly differentiated human prostatic adenocarcinoma cell line grown in nude mice) with concentrations in primary human adenocarcinomas. Following in vivo 1H NMR studies of DU 145 xenografts, citrate concentrations of DU 145 xenografts and surgically removed primary prostatic adenocarcinoma tissue were determined by quantitative high resolution 1H NMR and enzymatic assay. The most significant findings of this study were that citrate concentrations in primary human adenocarcinomas (3.74 +/- 0.19 mumol/g wet weight) were significantly lower than those observed for normal and benign hyperplastic (BPH) prostatic tissues. Furthermore there was a further ten-fold reduction of citrate associated with DU 145 xenografts (0.31 +/- 0.028 mumole/g wet weight) compared with primary prostatic cancer. DU 145 xenografts also exhibited higher levels of uridine diphosphosugars and choline containing metabolites relative to primary prostatic adenocarcinomas. These findings support the hypothesis that citrate is low in primary prostatic cancer and further reduced in metastatic disease.

Immunoperoxidase Staining of Acid Phosphatase in Human Prostatic Tissue

The introduction of immunoperoxidase and the indirect immunoperoxidase technique made important contributions in histopathologic diagnosis of prostatic cancer. This staining can be performed on formalin-fixed paraffin-embedded tissue which is usually available. We have used this histopathologic staining technique in 56 patients. The tissues include primary and metastatic prostatic cancer tissue in addition to normal renal pelvis and bladder tissue from other patients. Our data indicate that acid phosphatase can be localized in prostatic cells but not in transitional cells. Therefore, immunohistochemical staining of prostatic acid phosphatase seems most useful to identify metastatic prostate adenocarcinoma or primary tumor and to differentiate them from intraductal prostatic transitional carcinoma or other transitional cell carcinomas.