Bcl-2 expression delays mammary tumor development in dimethylbenz(a)anthracene-treated transgenic mice

Oncogene. 1999 Nov 11;18(47):6597-604. doi: 10.1038/sj.onc.1203099.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Apoptosis
  • Carcinogens / toxicity*
  • Cell Division / genetics
  • Genes, p53
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Transgenic
  • Milk Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Transgenes


  • Carcinogens
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • whey acidic proteins
  • 9,10-Dimethyl-1,2-benzanthracene