Bcl-2 accelerates multistep prostate carcinogenesis in vivo.
The impact of bcl-2 proto-oncogene expression on the pathogenesis and progression of prostate cancer was examined in a transgenic mouse model. Probasin-bcl-2 transgenic mice were crossed with TRAMP (TRansgenic Adenocarcinoma Mouse Prostate) mice that express the SV40 early genes (T/t antigens) under probasin control. Prostate size, cell proliferation, apoptosis, and the incidence and latency of tumor formation were evaluated. The double transgenic, probasin-bcl-2 X TRAMP F1 (BxT) mice exhibited an increase in the wet weight of the prostate. This was associated with an increase in proliferation, attributable to T/t antigens, and a decrease in apoptosis attributable to bcl-2. The latency to tumor formation was also decreased in the BxT mice compared to the TRAMP mice. The incidence of metastases was identical in both the TRAMP and BxT mice. Lastly, the incidence of hormone-independent prostate cancer was reduced in the BxT mice compared to the TRAMP mice. Together, these results demonstrate that bcl-2 can facilitate multistep prostate carcinogenesis in vivo.
Bruckheimer
E M
EM
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Brisbay
S
S
Johnson
D J
DJ
Gingrich
J R
JR
Greenberg
N
N
McDonnell
T J
TJ
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000727:Androgen-Binding Protein / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000502:physiology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D003433:Crosses, Genetic; D004247:DNA / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005816:Genetic Complementation Test; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009929:Organ Size; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
D000727:Androgen-Binding Protein; D000728:Androgens; D000952:Antigens, Polyomavirus Transforming; D019253:Proto-Oncogene Proteins c-bcl-2; C027519:probasin; D004247:DNA