Increased RB1 abnormalities in human primary prostate cancer following combined androgen blockade

Prostate. 1998 Feb 1;34(2):145-51. doi: 10.1002/(sici)1097-0045(19980201)34:2<145::aid-pros10>3.0.co;2-i.

Abstract

Background: The RB1 proliferation control pathway is a critical determinant of cell cycle progression. Abnormalities of RB1 are found in a variety of cancers, and the association with human prostate cancer (CaP) was examined here.

Methods: RNA expression levels of RB1 in CaPs were examined by RT-PCR. RNA integrity was assessed by evaluating expression of an endogenous gene standard.

Results: Abnormally low RB1 mRNA expression was found in 12/33 (36%) of CaPs from patients who had received combined androgen blockade (CAB) treatment. In contrast, 6/48 (13%) untreated CaPs showed abnormally low expression. This difference was statistically significant (P = 0.015). In the samples from untreated patients, a higher frequency of abnormal RB1 was found in specimens with a higher Gleason grade (P = 0.038). In addition, one untreated stage C, grade 9 specimen was found to express RB1 transcripts lacking exon 22, as determined by sequencing of DNA from the truncated transcripts.

Conclusions: These findings suggest that abnormalities of RB1 may contribute to hormone-withdrawal-related survival of CaP cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use*
  • Exons / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, Retinoblastoma / genetics*
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Male
  • Neoplasm Staging
  • Orchiectomy
  • Polymerase Chain Reaction
  • Prostate / chemistry
  • Prostate / pathology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / analysis
  • RNA, Neoplasm / genetics
  • Tumor Cells, Cultured

Substances

  • Androgen Antagonists
  • RNA, Messenger
  • RNA, Neoplasm
  • Gonadotropin-Releasing Hormone