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MGI Accession ID: MGI:3848592
J Number: J:149486
Other Accession IDs: Title: Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer.
Authors: Glover CE; Gurley KE; Kim KH; Storer B; Fero ML; Kemp CJ
Journal: Carcinogenesis
Volume: 30
Issue: 6
Date: 2009 Jun
Year: 2009
Pages: 1058-63
Review Status: Peer Reviewed

Abstract:

The cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) (p27) is a marker of prognosis in many cancers, including breast cancer. Low p27 expression correlates with poor prognosis, especially in hormone receptor positive breast tumors. This association suggests a role for p27 in hormone-dependent cancer. We used the Wnt-1 transgenic mouse model to further explore the role of p27 in hormone-driven breast cancer. We found that p27 deficiency did not alter breast cancer rate in either male or female Wnt-1 mice. However, we did find p27-/- females had reduced levels of serum progesterone (P) and increased variability in estradiol (E), which could have affected their cancer susceptibility. To equalize hormone levels, an additional cohort of Wnt-1 female mice was ovariectomized and implanted with slow release pellets of E and P. Although this treatment did not alter the breast cancer rate, it did accelerate the development of pituitary and gastric tumors in p27-/- mice. This study shows that while not a significant inhibitor of Wnt-1-driven breast cancer, p27 inhibits gastric tumors, whose latency is modulated by sex steroids.

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