期刊
ONCOGENE
卷 21, 期 42, 页码 6446-6457出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205892
关键词
Apc; Tcf-1; mammary; acanthoma; cre
资金
- Biotechnology and Biological Sciences Research Council [G06054] Funding Source: Medline
Apc (adenomatous polyposis colt) encodes a tumour suppressor gene that is mutated in the majority of colorectal cancers. Recent evidence has also implicated Apc mutations in the aetiology of breast tumours. Ape is a component of the canonical Wnt signal transduction pathway, of which one target is Tcf-1. In the mouse, mutations of both Ape and Tcf-1 have been implicated in mammary tumorigenesis. We have conditionally inactivated Apc in both the presence and absence of Tcf-1 to examine the function of these genes in both normal and neoplastic development. Mice harbouring mammary-specific mutations in Apc show markedly delayed development of the mammary ductal network. During lactation, the mice develop multiple metaplastic growths which, surprisingly, do not spontaneously progress to neoplasia up to a year following their induction. However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma.
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