Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.

Abstract	Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.
Authors	Nian-An Luo, Ya-Qi Qu, Guo-Dong Yang, Tao Wang, Ren-Li Li, Lin-Tao Jia, Rui Dong
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 11 Pg. 20306-20 (Nov 06 2014) ISSN: 1422-0067 [Electronic] Switzerland
PMID	25383675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	3' Untranslated Regions ELAV Proteins Lymphokines Platelet-Derived Growth Factor RNA, Messenger platelet-derived growth factor C
Topics	3' Untranslated Regions (genetics) Breast Neoplasms (genetics, pathology) Cell Line, Tumor ELAV Proteins (genetics, metabolism) Female Gene Expression Regulation, Neoplastic Humans Lymphokines (genetics, metabolism) Middle Aged Neoplasm Staging Platelet-Derived Growth Factor (genetics, metabolism) Prognosis RNA Stability (genetics) RNA, Messenger (genetics, metabolism) Stress, Physiological Transcription, Genetic Up-Regulation (genetics)

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