title: Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice.
abstract: 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.
authors.affiliation: Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Murphy
authors.forename: F S
authors.initials: FS
authors.lastname: Kittrell
authors.forename: J P
authors.initials: JP
authors.lastname: Gay
authors.forename: R
authors.initials: R
authors.lastname: Jäger
authors.forename: D
authors.initials: D
authors.lastname: Medina
authors.forename: J M
authors.initials: JM
authors.lastname: Rosen
mesh_terms: 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
chemical_list: D002273:Carcinogens; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C024471:whey acidic proteins; D015127:9,10-Dimethyl-1,2-benzanthracene