Ets2-dependent microenvironmental support of mouse mammary tumors

Abstract

Decreasing the amount of active mouse Ets2 transcription factor by half in mice or use of a MAP kinase insensitive hypomorphic targeted Ets2 allele restricts the appearance of transgenic mammary tumors caused by either Polyoma middle T antigen (PyMT) or activated Neu/ErbB2. In addition, the early growth of transplanted mammary tumors is limited by restricted Ets2 activity of the host. Here we have tested genetically, with the use of a conditional Ets2flox allele and tissue specific Cre recombinase expression, whether Ets2 also functions within tumor cells by inactivating Ets2 within mammary luminal epithelial cells from which transgenic PyMTY315/322F tumors arise. We find that inactivation of Ets2 within tumor cells has no effect on tumor appearance or growth. By contrast, complete inactivation of Ets2 in both epithelial and stromal cells moderates the early hyperplastic phase of tumor development and the time of tumor appearance but does not prevent tumor occurrence and has no detectable effect on tumor growth. Thus, Ets2 supports mammary tumors exclusively through their microenvironment.