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CDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Cancer

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dc.contributor.author Larson, Pamela S en_US
dc.contributor.author Schlechter, Benjamin L en_US
dc.contributor.author King, Chia-Lin en_US
dc.contributor.author Yang, Qiong en_US
dc.contributor.author Glass, Chelsea N en_US
dc.contributor.author Mack, Charline en_US
dc.contributor.author Pistey, Robert en_US
dc.contributor.author de las Morenas, Antonio en_US
dc.contributor.author Rosenberg, Carol L en_US
dc.date.accessioned 2012-01-09T20:53:12Z
dc.date.available 2012-01-09T20:53:12Z
dc.date.copyright 2008 en_US
dc.date.issued 2008-3-6 en_US
dc.identifier.citation Larson, Pamela S, Benjamin L Schlechter, Chia-Lin King, Qiong Yang, Chelsea N Glass, Charline Mack, Robert Pistey, Antonio de las Morenas, Carol L Rosenberg. "CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer" BMC Cancer 8:68. (2008) en_US
dc.identifier.issn 1471-2407 en_US
dc.identifier.uri http://hdl.handle.net/2144/2882
dc.description.abstract BACKGROUND. CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. METHODS. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. RESULTS. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CONCLUSION. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor. en_US
dc.description.sponsorship Department of Defense Breast Cancer Research Program (DAMD 17-99-1-9573); National Institutes of Health PHS (CA081078); LaPann Fund en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2008 Larson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title CDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Cancer en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2407-8-68 en_US
dc.identifier.pubmedid 18325103 en_US
dc.identifier.pmcid 2323395 en_US


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Copyright 2008 Larson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as Copyright 2008 Larson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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