Suppression of default apoptosis in androgen-dependent cells by testosterone-mediated bcl-2 expression.
BACKGROUND
The significance of apoptosis with regard to the development and progression of androgen-dependent cells has not been clearly understood. In the present study we investigated the expression of the bcl-2 proto-oncogene after androgen deprivation and its role in cell growth in an androgen-dependent cell line.


METHODS
We used SC2G, an androgen-dependent mouse mammary carcinoma cell line cloned from Shionogi carcinoma 115 (SC115). The expression of bcl-2 mRNA and protein in SC2G cells was measured by reverse transcription-polymerase chain reaction and western blotting, respectively. We also investigated the effects of antisense oligodeoxynucleotides (ODN) complementary to strategic sites in the mouse bcl-2 gene in SC2G cells.


RESULTS
When SC2G cells were cultured in serum-free medium, the number of viable cells was significantly larger among cells with testosterone than those without testosterone after 3 days. Apoptosis was demonstrated in approximately 30% of positive-staining nuclei in SC2G cells cultured in testosterone-free medium. The levels of bcl-2 mRNA and protein in SC2G cells started to decrease after testosterone withdrawal. The cell density of SC2G cells decreased after 4 days culture with antisense ODN when compared with cells cultured in the presence of sense control.


CONCLUSIONS
These data indicate that bcl-2 proto-oncogene inhibits the self-programmed apoptosis of androgen-dependent cells, suggesting the possibility of an antisense therapy for hormone-refractory prostate cancer, which is reported to express high levels of Bcl-2 protein.
Ohigashi
T
T
Department of Urology, Saitama Medical School, Japan. ohigashi@med.keio.ac.jp
Ueno
M
M
Iida
M
M
Hirata
R
R
Nakanoma
T
T
Deguchi
N
N
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D016375:Antisense Elements (Genetics); D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D016375:Antisense Elements (Genetics); D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013739:Testosterone