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Increased RB1 abnormalities in human primary prostate cancer following combined androgen blockade
P C Mack1, S G Chi, F J Meyers
1Department of Internal Medicine, University of California, Davis Cancer Center, Sacramento 95817, USA.
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.