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Depletion of nuclear SOX9 impairs differentiation & facilitates growth of invasive ductal breast carcinoma
Author(s) -
Chakravarty Geetika,
Moroz Krystof,
Lacey Michelle R,
Makridakis Nick M,
Agrawal Krishna,
Mondal Debasis
Publication year - 2010
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.24.1_supplement.754.4
Subject(s) - sox9 , breast cancer , cancer research , biology , gene knockdown , ductal carcinoma , breast carcinoma , sox2 , metastasis , cancer , pathology , medicine , embryonic stem cell , gene expression , gene , genetics
Invasive breast cancer growth is highly influenced by aberrations in genes controlling normal embryonic development. Recent reports have highlighted the role of Twist, FOXC2, SOX2 and SOX4 in breast cancer (BC) metastasis. But, the role of SOX9, a retinoid inducible gene, in modulating human BC progression remains unknown. SOX9 expression in human BC tissue micro arrays was assessed using immunohistochemistry and cDNA array data from published databases was analyzed for correlation of SOX9 with known poor prognostic parameters of BC. To confirm if deregulation of SOX9 function played a role in BC, genomic analysis of 17q24.3 region was carried out from samples of a large cohort of control and diseased Asian subjects. We found SOX9 expression to be higher in BC cell lines with stem like properties, cells of basal origin, ER negative and high grade human breast tumors. In addition to being associated with poor prognostic indicators of human BC, SOX9 was localized in the cytoplasm of 25–30% human ductal carcinomas and lymph node metastases. Its aberrant cytoplasmic localization or knockdown of its mRNA enhanced the proliferative potential of IDCs. Furthermore, SOX9 locus conferred predisposition to BC amongst Asian women. Our results suggest, SOX9 may functions as a tumor suppressor by promoting differentiation and its deregulation may contribute to the poor clinical outcome associated with invasive breast cancer.