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Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer.

Glover, Cynthia E. and Gurley, Kay E. and Kim, Kyung-Hoon and Storer, Barry and Fero, Mathew L. and Kemp, Christopher J. (2009) Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer. Carcinogenesis, 30 (6). pp. 1058-1063. ISSN 1460-2180

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Abstract

The cyclin dependent kinase (Cdk) inhibitor p27/Kip1 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 and increased variability in estradiol, 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 estradiol and progesterone. 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.

Item Type: Article
Additional Information: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Carcinogenesis following peer review. The definitive publisher-authenticated version (currently epub ahead of print) is available online at: http://carcin.oxfordjournals.org/cgi/reprint/bgp089v1
DOI: 10.1093/carcin/bgp089
PubMed ID: 19380520
PMCID: PMC2691144
Keywords or MeSH Headings: * Animals * Cyclin-Dependent Kinase Inhibitor p27/genetics * Cyclin-Dependent Kinase Inhibitor p27/metabolism* * Estradiol/blood* * Estradiol/pharmacology * Female * Male * Mammary Neoplasms, Experimental/blood* * Mammary Neoplasms, Experimental/pathology * Mice * Mice, Knockout * Neoplasms, Hormone-Dependent/blood* * Neoplasms, Hormone-Dependent/pathology * Ovariectomy * Pituitary Neoplasms/metabolism * Pituitary Neoplasms/pathology * Progesterone/metabolism* * Progesterone/pharmacology * Stomach Neoplasms/metabolism * Stomach Neoplasms/pathology * Wnt1 Protein/genetics * Wnt1 Protein/metabolism*
Subjects: Diseases > Solid tumors > Digestive system cancer
Diseases > Solid tumors > Breast cancer
Molecules > Hormones
Cellular and Organismal Processes > Genetic processes > Transcription
Molecules > Proteins > Cell cycle proteins
Depositing User: Library Staff
Date Deposited: 14 May 2009 23:02
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/288

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