Carcinogen 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis is accelerated in Smad3 heterozygous mice compared to Smad3 wild type mice

Oncotarget. 2016 Oct 4;7(40):64878-64885. doi: 10.18632/oncotarget.11713.

Abstract

Previous studies based on cell culture and xenograft animal models suggest that Smad3 has tumor suppressor function for breast cancer during early stages of tumorigenesis. In this report, we show that DMBA (7,12-dimethylbenz[a]anthracene), a chemical carcinogen, induces mammary tumor formation at a significantly higher frequency in the Smad3 heterozygous mice than in the Smad3 wild type mice. This is the first genetic evidence showing that Smad3 inhibits mammary tumor formation in a mouse model. Our findings support the notion that Smad3 has important tumor suppressor function for breast cancer.

Keywords: DMBA; Smad3; TGF-ß; breast cancer; carcinogenesis.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Animals
  • Carcinogenesis* / genetics
  • Carcinogens / toxicity
  • Female
  • Heterozygote
  • Male
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Carcinogens
  • Smad3 Protein
  • Smad3 protein, mouse
  • Tumor Suppressor Proteins
  • 9,10-Dimethyl-1,2-benzanthracene