The Cell of Breast Cancer Origin Affects Tumor Estrogen Receptor Status.

Abstract

Abstract It has been known for some time that breast cancer phenotype is dependent upon the initiating oncogene. However, it has only recently been demonstrated that breast cancer phenotype, including tumor histopathology, gene expression profile, and metastatic potential, may also depend upon the cellular subtype from which a tumor arises. Breast tumor estrogen receptor (ER) status is a common prognostic factor, and approximately 70% of all breast tumors are ER+; that is, they expresse ER in ≥5% of tumor cells. However, it remains unknown which factors determine breast cancer ER status. It is possible that the cell of tumor origin plays a role in determining the ER status of the resulting tumor. Our lab has developed a method to somatically introduce oncogenes into a developmentally normal mouse mammary gland with temporal control using the modified avian retrovirus RCAS. We have generated transgenic mice that express the RCAS receptor TVA under mammary cell selective markers and demonstrated our ability to infect individual cells and induce mammary tumors. In this study we used an RCAS vector encoding polyoma virus middle T antigen (PyMT) to infect transgenic adult MMTV-tva or WAP-tva mice. The MMTV LTR is though to be active in several different mammary cell types including luminal epithelial, progenitor, and stem cells. WAP is primarily active in more highly differentiated mammary epithelial cells. Tumors induced by RCAS-PyMT differ in histopathology between the two lines. Those arising in MMTV-tva mice have a predominately solid morphology, while those arising in WAP-tva mice display a predominately papillary morphology. Interestingly, we found that the majority of tumors arising in MMTV-tva mice are ER+ (61%), while tumors arising in WAP-tva mice are predominately ER- (95%). Our data suggest that tumors induced by the same oncogene from distinct cellular subtypes in the mouse mammary epithelium can significantly vary in histopathology, and that tumor ER status can be dependent upon the cell of tumor origin. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2163.