Developing a Novel Mouse Model for Breast Cancer by Targeting Oncogenes to Mammary Progenitor Cells.

摘要

Mouse models are very valuable for preclinical testing of new therapeutic drugs against breast cancer and for studying how breast cancer cells invade and spread, but most mammary tumors arising in mice are different from human breast cancer. Most mouse models are created by targeting oncogenic lesions primarily to the more mature differentiated breast cells. Clinical breast cancer, however, are believed to arise from undifferentiated progenitor cells. Therefore, if we can induce mouse breast tumors specifically from progenitor cells, we may be able to produce models that more closely resemble human breast cancer. No promoter that is exclusively expressed in the mammary progenitor cells has yet been reported, but the promoter of keratin 6 is a likely candidate. In order to determine whether keratin 6 is indeed a progenitor cell marker, and whether targeting oncogenes to progenitor cells may yield better models, we have succeeded in creating a BAC transgenic line expressing from the keratin 6 promoter the TVA viral receptor, for selective targeting of reporters and oncogenes using a viral vector RCAS. Next, we will use this line of mice to determine whether these K6-positive cells are indeed progenitor cells, and whether they will give rise to tumors that better resemble human breast cancers.