Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice.
Bcl-2 is known to have dual antiproliferative and antiapoptotic roles. Overexpression of Bcl-2 in the mammary gland using a whey acidic protein (WAP) promoter-driven Bcl-2 transgene inhibits apoptosis in the mammary gland during pregnancy, lactation, and involution, and also counteracts apoptosis induced by overexpression of a mutant p53 transgene (WAP-p53 172 R-L). WAP-Bcl-2 mice and nontransgenic controls were treated with the carcinogen dimethylbenz(a)anthracene (DMBA). Surprisingly, the nontransgenic mice developed mammary tumors with decreased latency. Tumors arising in WAP-Bcl-2 mice displayed substantially reduced levels of proliferation relative to those seen in nontransgenic mice (P < 0.015), perhaps resulting in the observed increase in tumor latency following carcinogen treatment. This WAP-Bcl-2 mouse tumor model reflects the situation seen in some human breast cancers overexpressing Bcl-2, where expression of Bcl-2 has been shown to correlate with a lower proliferative index in tumors.
Murphy
K L
KL
Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Kittrell
F S
FS
Gay
J P
JP
Jäger
R
R
Medina
D
D
Rosen
J M
JM
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000235:genetics; D016158:Genes, p53; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D019076:Transgenes
D002273:Carcinogens; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C024471:whey acidic proteins; D015127:9,10-Dimethyl-1,2-benzanthracene