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Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers
Annual rept. 1 Jun 2011-31 May 2012
WAYNE STATE UNIV DETROIT MI
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Amplification of 8p11-12 occurs in approximately 15 of human breast cancer HBC, and this region of amplification is significantly associated with disease-specific survival and distant recurrence in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon for identifying candidate oncogenes in breast cancer. We identified Wolf-Hirschhorn syndrome candidate 1-like 1 WHSC1L1 as a candidate oncogene based on statistical analysis of copy number increase and overexpression. In this study, we demonstrated that WHSC1L1 acts as a transforming gene stable WHSC1L1 overexpression in nontumorigenic MCF10A cells induces transformed phenotypes, whereas WHSC1L1 knockdown in 8p12 amplified, ER-positive breast cancer cells inhibits proliferation in vitro. We also found that overexpression of WHSC1L1 likely induces the acquisition of stem cell-like properties in vitro. WHSC1L1 family proteins have recently been shown to bind methylated histones, specifically H3K36 methylation marks. Thus WHSC1L1 may contribute to transformation through the alteration of epigenetic histone marks in a subset of aggressive breast cancers. We published 2 research papers and 1 abstract based on this award in the past year.
APPROVED FOR PUBLIC RELEASE