Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas

Abstract

The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short-sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma. We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short-sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short-sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA-PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.

Loss of the retinoblastoma susceptibility gene (RB1) is a frequent and early event in prostatic tumorigenesis

“…Loss of heterozygosity within the RBl gene was identified in 60% of prostate cancers, which is higher than has previously been reported (Carter et al, 1990;Macoska et al, 1992; Sarkar et al (1992) looked for deletions within the DNA of the RBl promoter region and within exon 21 mRNA. They found an abnormal short-sized mRNA transcript of RB1 exon 21 extracted from a pure population of cells in tissue culture (cell line DU 145), but not in their seven cancer cases.…”

Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding

“…However, D EcoRI (1 ± 302) was not captured by any of these RB proteins. The RB D Exon 21 mutation corresponds to the RB mutation found in DU-145 cells (Sarkar et al, 1992).…”

Detection and expression of human BK virus sequences in neoplastic prostate tissues

“…Mutations in the Rb1 gene are infrequent in PCA (Bookstein et al, 1990;Sarkar et al, 1992;Melamed et al, 1997;reviewed in Abate-Shen and Shen, 2000). Although the mutation rate of the p53 gene in PCA is also low, p53 inactivation has been implicated in PCA progression (Bookstein et al, 1993;Bauer et al, 1995;Brewster et al, 1999;Osman et al, 1999;reviewed in Abate-Shen and Shen, 2000).…”