This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jagadeesh, S. Articles by Banerjee, P. P. Search for Related Content PubMed PubMed Citation Articles by Jagadeesh, S. Articles by Banerjee, P. P.

Genistein Represses Telomerase Activity via Both Transcriptional and Posttranslational Mechanisms in Human Prostate Cancer Cells

¹ Department of Cell Biology, Georgetown University Medical Center, Washington, District of Columbia; and ² Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Takaramachi, Kanazwa, Ishikawa, Japan

Requests for reprints: Partha P. Banerjee, Department of Cell Biology, Georgetown University Medical Center, 3900 Reservoir Road, Northwest, Washington, DC 20057. Phone: 202-687-8611; Fax: 202-687-1823; E-mail: ppb{at}georgetown.edu.

Genistein, the most abundant isoflavone present in soybean has antiproliferative effects on a variety of cancer cells, including prostate cancer. However, the molecular mechanism of antiproliferative effects of genistein is not entirely understood. Because the activation of telomerase is crucial for cells to gain immortality and proliferation ability, we examined the role of genistein in the regulation of telomerase activity in prostate cancer cells. Here, we show that genistein-induced inhibition in cell proliferation is associated with a reduction in telomerase activity. Using reverse transcriptase-PCR and hTERT promoter activity assays, we showed that genistein decreased hTERT expression and transcriptional activity dose-dependently. Using various deleted hTERT promoter constructs, we defined that the hTERT core promoter is enough to observe the genistein-induced repression of hTERT transcriptional activity. Because c-Myc is involved in transcriptional regulation of hTERT, c-Myc expression was examined. A dose-dependent decrease in c-Myc message and proteins was observed with genistein treatment. These results indicate that genistein represses hTERT transcriptional activity via the down-regulation of c-Myc expression. However, genistein-induced repression of hTERT transcriptional activity was not blocked by the mutation of c-Myc at the hTERT promoter, suggesting that additional factors are involved in genistein-dependent repression of telomerase activity. Interestingly, we observed that genistein down-regulates the activation of Akt thereby phosphorylation of hTERT and inhibits its translocation to the nucleus. These results show for the first time that genistein represses telomerase activity in prostate cancer cells not only by repressing hTERT transcriptional activity via c-Myc but also by posttranslational modification of hTERT via Akt. (Cancer Res 2006; 66(4): 2107-15)

This article has been cited by other articles:

				J.-l. Zhang, Y. Fu, L. Zheng, W. Li, H. Li, Q. Sun, Y. Xiao, and F. Geng Natural isoflavones regulate the quadruplex-duplex competition in human telomeric DNA Nucleic Acids Res., May 1, 2009; 37(8): 2471 - 2482. [Abstract] [Full Text] [PDF]

				M. ZAVLARIS, K. ANGELOPOULOU, I. VLEMMAS, and N. PAPAIOANNOU Telomerase Reverse Transcriptase (TERT) Expression in Canine Mammary Tissues: A Specific Marker for Malignancy? Anticancer Res, January 1, 2009; 29(1): 319 - 325. [Abstract] [Full Text] [PDF]

				S. A. Gatz and L. Wiesmuller Take a break--resveratrol in action on DNA Carcinogenesis, February 1, 2008; 29(2): 321 - 332. [Abstract] [Full Text] [PDF]

				M. N. Chau, L. H. El Touny, S. Jagadeesh, and P. P. Banerjee Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3 Carcinogenesis, November 1, 2007; 28(11): 2282 - 2290. [Abstract] [Full Text] [PDF]