Transgenic mice reveal roles for TGFα and EGF receptor in mammary gland development and neoplasia

摘要: Transforming growth factor-alpha (TGFα)4 and/or the EGF receptor (EGFR) are frequently overexpressed by human and rodent breast tumors, as well tumor-derived cell lines. Additionally, various observations suggest a role for TGFα EGFR signaling system in normal mouse mammary gland development. Recently, several laboratories have established transgenic mice with which to study of this factor neoplastic biology. Examination these revealed that overexpression has profound consequences tissue. Most strikingly, expressing under control tissue-specific nonspecific promoters stochastically developed focal tumors an incidence latency was markedly affected pregnancy. TGFα-induced were well-differentiated adenomas/adenocarcinomas, although some undifferentiated locally invasive. Distant metastases only occasionally observed. Administration genotoxic carcinogen, 7,12-dimethylbenzanthracene (DMBA), dramatically accelerated tumorigenesis induced transgene, raising possibility acts promoter Mice harboring dual transgenes encoding either wild-type ERBB2 or c-myc displayed compared carrying any single alone, indicative potent cooperativity. Moreover, bitransgenic less dependent on pregnancy, generally more malignant appearance. Finally, also dynamics. consistently precocious alveolar development, variably impaired respect lactation, showed reduced postlactional involution. As result, glands multiparous females accumulated hyperplastic lesions resembled milk-producing alveoli. Limited data support hypothesis precursors tumors. In summary, findings underscore potential importance cellular differentiation transformation gland. They establish powerful model molecules dynamic