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Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells.

Publication ,  Journal Article
Guo, C; Geverd, D; Liao, R; Hamad, N; Counter, CM; Price, DT
Published in: J Urol
August 2001

PURPOSE: Telomerase, the enzyme that catalyzes the elongation of telomeres, is illegitimately activated in the majority of cancers, including that of the prostate, where it may greatly extend the life span of malignant cells. The inhibition of telomerase by molecular intervention has been shown to lead eventually to cell death in several tumor or in vitro immortalized cell lines and in 1 case prevent tumor growth in vivo. Therefore, we tested whether a similar strategy may be used to limit the tumorigenic potential of late stage prostate cancer cells. MATERIALS AND METHODS: PC-3, LNCaP and DU-145 human prostate cancer cells were infected with a retrovirus encoding a dominant-negative version of the catalytic subunit of telomerase (DN-hTERT). Subclones or polyclonal populations were assayed for DN-hTERT expression, telomerase activity, telomere length, cell life span and in most cases tumorigenicity in nude mice. RESULTS: DN-hTERT expression levels directly correlated with cell life span and tumorigenic growth. PC-3 cells expressing high levels of DN-hTERT died rapidly and failed to form tumors in nude mice, whereas cells expressing the lowest levels proliferated the longest and generated tumors that later spontaneously regressed. Similarly the inhibition of telomerase activity in LNCaP cells was greater than in DU-145 cells and correspondingly LNCaP cells had a shorter life span. CONCLUSIONS: DN-hTERT expression limits the life span and tumorigenic potential of human prostate cancer cells, although the onset of these effects appears to be dictated by the expression level of DN-hTERT. Therefore, telomerase represents an attractive target for potentially managing prostate cancer. Nevertheless, effective means of inhibiting the enzyme may be required for a therapeutically useful outcome.

Duke Scholars

Published In

J Urol

ISSN

0022-5347

Publication Date

August 2001

Volume

166

Issue

2

Start / End Page

694 / 698

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Telomerase
  • Prostatic Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans
 

Citation

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Guo, C., Geverd, D., Liao, R., Hamad, N., Counter, C. M., & Price, D. T. (2001). Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells. J Urol, 166(2), 694–698.
Guo, C., D. Geverd, R. Liao, N. Hamad, C. M. Counter, and D. T. Price. “Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells.J Urol 166, no. 2 (August 2001): 694–98.
Guo C, Geverd D, Liao R, Hamad N, Counter CM, Price DT. Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells. J Urol. 2001 Aug;166(2):694–8.
Guo, C., et al. “Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells.J Urol, vol. 166, no. 2, Aug. 2001, pp. 694–98.
Guo C, Geverd D, Liao R, Hamad N, Counter CM, Price DT. Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells. J Urol. 2001 Aug;166(2):694–698.
Journal cover image

Published In

J Urol

ISSN

0022-5347

Publication Date

August 2001

Volume

166

Issue

2

Start / End Page

694 / 698

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Telomerase
  • Prostatic Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans