Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer.
The significance of apoptosis in relation to the development and progression of prostate cancer remains largely undefined. bcl-2 is an oncogene that functions by overriding apoptosis. bcl-2 expression was localized to the basal epithelial cells in the normal human prostate with the use of immunohistochemistry. Androgen-dependent and androgen-independent prostate carcinomas were evaluated immunohistochemically for bcl-2 expression. bcl-2 was undetectable in 13 of 19 cases of androgen-dependent cancers. In contrast, androgen-independent cancers displayed diffuse, high levels of bcl-2 staining (P < 0.01). In rats, steady-state levels of bcl-2 mRNA, assessed by S1 assays, reached maximum levels 10 days following castration. Addition of exogenous testosterone with, or without, flutamide demonstrated that the increased bcl-2 mRNA resulted from androgen ablation. Our findings indicate that bcl-2 expression is augmented following androgen ablation and is correlated with the progression of prostate cancer from androgen dependence to androgen independence.
McDonnell
T J
TJ
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Troncoso
P
P
Brisbay
S M
SM
Logothetis
C
C
Chung
L W
LW
Hsieh
J T
JT
Tu
S M
SM
Campbell
M L
ML
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000209:etiology; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D051381:Rats; D017207:Rats, Sprague-Dawley
D000728:Androgens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2