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CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer

Pamela S Larson1, Benjamin L Schlechter, Chia-Lin King

  • 1Department of Pathology and Laboratory Medicine, Boston University Medical Center, Boston, MA, USA. pamkent@bu.edu

BMC Cancer
|March 8, 2008
PubMed
Abstract

Insights

CDKN1C (p57KIP2) expression decreases in most breast cancers at both mRNA and protein levels. This reduction is not due to gene mutation, suggesting CDKN1C may act as a tumor suppressor in breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • CDKN1C (p57KIP2) is a cyclin-dependent kinase inhibitor with limited known involvement in breast cancer.
  • Its family members are implicated in breast cancer, prompting investigation into CDKN1C's role.
  • Hypothesis: Decreased CDKN1C expression contributes to breast carcinogenesis.

Purpose of the Study:

  • To investigate the role of CDKN1C in breast cancer development.
  • To determine if CDKN1C expression is altered in breast tumors.
  • To explore the mechanism of CDKN1C alteration in breast carcinogenesis.

Main Methods:

  • Analyzed allele imbalance/loss of heterozygosity (AI/LOH) of CDKN1C and the 11p15.5 region in 82 breast cancers.
  • Quantified CDKN1C mRNA levels using qPCR in 10 cancers.
  • Assessed CDKN1C protein levels via immunohistochemistry in 20 cancers, using laser microdissection for all samples.

Main Results:

  • AI/LOH at 11p15.5 occurred in 38% of cancers, but CDKN1C itself showed AI/LOH in only 19%.
  • CDKN1C mRNA levels were reduced in 90% of cancers (2-60% of normal levels).
  • CDKN1C protein was decreased in ductal carcinoma in situ (50%) and invasive carcinoma (28%), primarily due to loss of expression in myoepithelial cells.

Conclusions:

  • CDKN1C is expressed in normal breast epithelium, predominantly in myoepithelial cells.
  • A significant decrease in both mRNA and protein levels of CDKN1C occurs in most breast cancers.
  • The reduction in CDKN1C is not mediated by AI/LOH, suggesting a tumor suppressor role for CDKN1C in breast cancer.

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