The impact of bcl-2 expression and bax deficiency on prostate homeostasis in vivo.
Prostatic glandular epithelial cells undergo apoptosis in response to androgen-deprivation. The molecular determinants of androgen-responsiveness in these cells are incompletely understood. Recent evidence suggests that bcl-2 gene family members may be important in this context. We used the probasin promoter to target a human bcl-2 transgene specifically to the prostate in order to assess its impact on conferring resistance to androgen withdrawal in, otherwise sensitive, prostatic glandular epithelial cells in vivo. We examined the contribution of bax to mediating androgen-responsiveness in prostatic glandular epithelial cells using bax knockout mice. The histologic appearance of the prostates from probasin-bcl-2 transgenic mice or bax-/- mice did not differ from those of control littermates. There was no evidence of hyperplastic or neoplastic growth. There was no difference between probasin bcl-2 transgenic mice, bax-/- mice, and control littermates in steady-state levels of apoptosis. Following castration our findings suggest that both bax and bcl-2 may each contribute to the androgen-responsiveness of prostatic glandular epithelial cells. It is apparent from these results, however, that bax is not required to mediate cell death in prostatic glandular epithelial cells following castration. A comparison between the apoptotic indices in the ventral prostate from the probasin-bcl-2 and bax-/- mice following castration suggests that the presence of bcl-2 may be a more important indicator of androgen-sensitivity than a deficiency of bax.
Bruckheimer
E M
EM
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Cho
S
S
Brisbay
S
S
Johnson
D J
DJ
Gingrich
J R
JR
Greenberg
N
N
McDonnell
T J
TJ
D000727:Androgen-Binding Protein / Q000235:genetics; D000728:Androgens / Q000172:deficiency; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009919:Orchiectomy; D011467:Prostate / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051028:bcl-2-Associated X Protein
D000727:Androgen-Binding Protein; D000728:Androgens; C494826:BAX protein, human; C494827:Bax protein, mouse; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C027519:probasin