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Obscurins: Giant proteins with tumor suppressing activities in breast cancer
Author(s) -
Perry Nicole Alana,
Shriver Marey,
Mameza Marie,
Grabias Bryan,
Balzer Eric,
Kontrogianni-Konstantopoulos Aikaterini
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1065.4
Subject(s) - biology , apoptosis , cancer research , breast cancer , programmed cell death , colorectal cancer , gene , cancer , cell growth , cancer cell , microbiology and biotechnology , genetics
Obscurins (~70–870 kDa) are cytoskeletal proteins originally identified in striated muscles where they hold structural and regulatory roles. Recently, analysis of 13,023 genes in breast and colorectal cancers identified OBSCN as one of the most frequently mutated genes, implicating it in cancer formation and progression. Herein, we studied the expression profile of obscurins in breast, colon and skin cancer cell lines, and their involvement in cell growth. Immunoblot analysis demonstrated significant reduction of obscurin proteins in cancer cell lines. MCF10A breast epithelial cells treated with shRNAs targeting obscurins exhibited significantly increased survival and reduced apoptosis accompanied by moderate anchorage independent growth, following exposure to the DNA damaging agent etoposide. Quantitative RT‐PCR indicated that the anti‐apoptotic genes Bag‐4 and HAX‐1 were up‐regulated in MCF10A obscurin‐null cells, whereas initiator caspase‐9 and death caspase‐3 transcripts were down‐regulated. Our findings are the first to pinpoint critical roles for obscurins in cancer development by contributing to the regulation of cell survival and apoptosis.