Growth inhibitory effect of Krüppel-like factor 6 on human prostatic carcinoma and renal carcinoma cell lines.

Kidney and prostate cancers are leading causes of death in the world, and accumulating evidence suggests that tumor suppressor gene, Krüppel-like factor 6 (KLF6), plays an important role in both the development and the progression of cancer. However, the effect of wild type KLF6 (wtKLF6) on the growth potential of renal carcinoma cells has not been examined. In the present study, we therefore introduced wtKLF6 gene into a prostatic carcinoma derived cell line, DU145, and a renal carcinoma derived cell line, OS-RC-2, and have established DU145-KLF6 and OS-RC-2-KLF6 cell lines, both of which stably over-express KLF6. Compared with vector-transfected cell lines (control cells), the wtKLF6-transfected cell lines showed the lower proliferation capacity (p < 0.01) and higher percentages of cells with apoptotic signals (p < 0.01). Moreover, the KLF6-overexpressed cell lines showed significant increases in the cell population at G0/G1 phase and significant decreases in the cell population at S and G2/M phases. There was no significant difference in the results of the cell cycle analysis between the two KLF6-overexpressed cell lines, DU145-KLF6 and OS-RC-2-KLF6. The cyclin-dependent kinase inhibitor p21 as a transcriptional target of the KLF6 gene was also studied. The expression levels of p21 mRNA and protein were up-regulated in both KLF6-overexpressed cell lines. These results indicate that the wtKLF6 gene effectively inhibited the growth of the prostatic carcinoma DU145 and renal carcinoma OS-RC-2 cell lines, probably through up-regulation of p21. Thus, KLF6 may represent a novel therapeutic target for inhibiting prostate and renal cancer.

[Effects of 4-hydroxytamoxifen on prostate smooth muscle cells: an in vitro experiment].

OBJECTIVE: To investigate the effects of 4- hydroxytamoxifen (OHT) on the proliferation and apoptosis of prostate smooth muscle cells and the expression of estrogen receptor (ER) and androgen receptor (AR). METHODS: Prostate smooth muscle cells were isolated from the resected specimens of prostate glands of 10 patients with benign prostatic hypertrophy (BPH), cultured, and exposed to estradiol (E(2)), diethylstilbestrol (DES), and OHT of different concentrations (1 x 10(-8) - 1 x 10(-5) mol/L) or mixture of E(2) (1 x 10(-8) - 1 x 10(-6) mol/L) with OHT (1 x 10(-7) mol/L). Flow cytometry was used to test the proliferation and apoptosis of the cells, and immunocytochemistry was used to test the expression of estrogen and androgen receptors. RESULTS: E(2) and DES promoted the proliferation of the prostate smooth muscle cells in a certain concentration range, but not dose-dependently, and OHT at the concentration of 1 x 10(-8) mol/L slightly increased the G(2)-M peak rate of the prostate smooth muscle cells, but suppressed the G(2)-M peak rate dose-dependently when its concentration was >or= 1 x 10(-7) mol/L (P < 0.05) and this suppression effect was dose-dependently (r = -0.312, P = 0.011). E(2) at the concentration >or= 1 x 10(-5) mol/L and DES at the concentration >or= 1 x 10(-6) mol/L slightly promoted the apoptosis of the prostate smooth muscle cells, but not dose-dependently, and OHT at the concentrations from 1 x 10(-8) mol/L to 1 x 10(-5) mol/L promoted the apoptosis of the prostate smooth muscle cells dose-dependently (r = 0.363, P = 0.021) and this effect could not be reversed by administration of E(2) at the concentration 1 x 10(-8) - 1 x 10(-6) mol/L (P > 0.05). E(2), DES, and OHT of different concentrations all increased the ERalpha and AR positive staining rates of the prostate smooth muscle cells (all P < 0.05). CONCLUSIONS: OHT suppresses the proliferation and promotes the apoptosis of prostate smooth muscle cells, and these functions do not depend on the estrogen receptor pathway. Low blood OHT concentration after oral administration of TAM and up-regulation of estrogen receptors by OHT may be the caused of the inefficiency of TAM for treatment of BPH.

[Effects of 40H-tamoxifen on the proliferation and apoptosis of prostate stromal cells].

OBJECTIVE: To investigate the effects of 4OH-Tamoxifen (OHT) on proliferation and apoptosis of primary cultured prostate stromal cells. METHODS: Primarily cultured prostate stromal cells in vitro were treated with various concentrations (10(-8) mol/L - 10(-5) mol/L) of estradiol (E2), diethylstilbestrol (DES), OHT and the mixture of E2 (10(-8) mol/L - 10(-6) mol/L) with OHT (10(-7) mol/L) and then MTT and TUNEL were used to detect their proliferation and apoptosis respectively. RESULTS: There was a significant difference (P < 0.05) between OHT and estrogens in the effects on the apoptosis and proliferation of the primarily cultured prostate stromal cells. OHT suppressed proliferation of the prostate stromal cells at the concentrations from 10(-7) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = -0.383, P = 0.005); OHT (10(-7) mol/L) suppressed the proliferation stimulation effect of E2 at the concentrations from 10(-8) mol/L to 10(-6) mol/L (P < 0.05). OHT induced apoptosis at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = 0.349, P = 0.012). The apoptosis induced by OHT could not be reversed by E2 at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P > 0.05). CONCLUSION: OHT can obviously suppressed the proliferation and promote the apoptosis of primarily cultured prostate stromal cells, which might not be totally attributed to the competitive inhibition of the estrogen receptor.

Dorsal penile nerves and primary premature ejaculation.

BACKGROUND: Based on our clinical experience, the number of dorsal penile nerves in patients with primary premature ejaculation (PPE) is not consistent with the average number (2 branches). In this study, we evaluated the number and distribution of dorsal penile nerves among healthy Chinese adults and patients with PPE. METHODS: The dorsal nerve of the penis, the deep dorsal vein of the penis, and the dorsal artery of the penis between the deep fascia of the penis and the albuginea penis were carefully educed, observed, and counted in 38 adult autopsy specimens. The number and distribution of the dorsal penile nerve in 128 surgical patients with PPE were determined. RESULTS: The numbers of dorsal penile nerves of the 38 cases were as follows: 7 branches in 1 case; 6 branches in 1 case; 5 branches in 6 cases; 4 branches in 9 cases; 3 branches in 14 cases; and 2 branches in 7 cases. Most of the dorsal nerves were parallel to each other and in the dorsum of the penis. In only 8 cases, the branches were connected by some communicating branches. In 4 cases, 1 or 2 thin dorsal nerves continued their pathway over the ventral aspect of the penis. The average number of branches of the dorsal penile nerve in patients with PPE was 7.16. CONCLUSIONS: Based on the study of 38 cases, the average number of dorsal penile nerves was 3.55 branches and that of patients with PPE was greater. These preliminary results suggest that the excessive dorsal penile nerves may have an impact on PPE via increased sensitivity and provide topographic data for the possible treatment of PPE.