Aging Mouse Models Reveal Complex Tumor-Microenvironment Interactions in Cancer Progression

Front Cell Dev Biol. 2018 Mar 29:6:35. doi: 10.3389/fcell.2018.00035. eCollection 2018.

Abstract

Mouse models and genetically engineered mouse models (GEMM) are essential experimental tools for the understanding molecular mechanisms within complex biological systems. GEMM are especially useful for inferencing phenocopy information to genetic human diseases such as breast cancer. Human breast cancer modeling in mice most commonly employs mammary epithelial-specific promoters to investigate gene function(s) and, in particular, putative oncogenes. Models are specifically useful in the mammary epithelial cell in the context of the complete mammary gland environment. Gene targeted knockout mice including conditional targeting to specific mammary cells can reveal developmental defects in mammary organogenesis and demonstrate the importance of putative tumor suppressor genes. Some of these models demonstrate a non-traditional type of tumor suppression which involves interplay between the tumor susceptible cell and its host/environment. These GEMM help to reveal the processes of cancer progression beyond those intrinsic to cancer cells. Furthermore, the, analysis of mouse models requires appropriate consideration of mouse strain, background, and environmental factors. In this review, we compare aging-related factors in mouse models for breast cancer. We introduce databases of GEMM attributes and colony functional variations.

Keywords: aging; gene knockout mice; genetically engineered mouse models (GEMMs); mammary tumorigenesis; mouse strain.

Publication types

  • Review