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dc.contributor.authorLarson, Pamela Sen_US
dc.contributor.authorSchlechter, Benjamin Len_US
dc.contributor.authorKing, Chia-Linen_US
dc.contributor.authorYang, Qiongen_US
dc.contributor.authorGlass, Chelsea Nen_US
dc.contributor.authorMack, Charlineen_US
dc.contributor.authorPistey, Roberten_US
dc.contributor.authorde las Morenas, Antonioen_US
dc.contributor.authorRosenberg, Carol Len_US
dc.date.accessioned2012-01-09T20:53:12Z
dc.date.available2012-01-09T20:53:12Z
dc.date.copyright2008en_US
dc.date.issued2008-3-6en_US
dc.identifier.citationLarson, 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.issn1471-2407en_US
dc.identifier.urihttp://hdl.handle.net/2144/2882
dc.description.abstractBACKGROUND. 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.sponsorshipDepartment of Defense Breast Cancer Research Program (DAMD 17-99-1-9573); National Institutes of Health PHS (CA081078); LaPann Funden_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.rightsCopyright 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.urihttp://creativecommons.org/licenses/by/2.0en_US
dc.titleCDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Canceren_US
dc.typearticleen_US
dc.identifier.doi10.1186/1471-2407-8-68en_US
dc.identifier.pubmedid18325103en_US
dc.identifier.pmcid2323395en_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.