MPA/DMBA-driven mammary carcinomas

Methods Cell Biol. 2021;163:1-19. doi: 10.1016/bs.mcb.2020.08.003. Epub 2020 Oct 1.

Abstract

The polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA, D) administered per os to wild-type female mice bearing slow-release medroxyprogesterone (MPA, M) pellets s.c. drives the formation of mammary carcinomas that recapitulate numerous immunobiological features of human luminal B breast cancer. In particular, M/D-driven mammary carcinomas established in immunocompetent C57BL/6 female mice (1) express hormone receptors, (2) emerge by evading natural immunosurveillance and hence display a scarce immune infiltrate largely polarized toward immunosuppression, (3) exhibit exquisite sensitivity to CDK4/CDK6 inhibitors, and (4) are largely resistant to immunotherapy with immune checkpoint blockers targeting PD-1. Thus, M/D-driven mammary carcinomas evolving in immunocompetent female mice stand out as a privileged preclinical platform for the study of luminal B breast cancer. Here, we provide a detailed protocol for the establishment of M/D-driven mammary carcinomas in wild-type C57BL/6 female mice. This protocol can be easily adapted to generate M/D-driven mammary carcinomas in female mice with most genetic backgrounds (including genetically-engineered mice).

Keywords: Chemotherapy; Immunotherapy; KRAS; PI3K; Radiation therapy; Targeted anticancer agents.

Publication types

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

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Breast Neoplasms* / drug therapy
  • Carcinoma*
  • Female
  • Humans
  • Mammary Neoplasms, Experimental* / chemically induced
  • Mammary Neoplasms, Experimental* / drug therapy
  • Medroxyprogesterone Acetate
  • Mice
  • Mice, Inbred C57BL

Substances

  • 9,10-Dimethyl-1,2-benzanthracene
  • Medroxyprogesterone Acetate