Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells.

Abstract	Cancer cells often develop drug resistance. In cisplatin-resistant HeLa cisR cells, fibroblast growth factor 13 (FGF13/FHF2) gene and protein expression was strongly upregulated, and intracellular platinum concentrations were kept low. When the FGF13 expression was suppressed, both the cells' resistance to platinum drugs and their ability to keep intracellular platinum low were abolished. Overexpression of FGF13 in parent cells led to greater resistance to cisplatin and reductions in the intracellular platinum concentration. These cisplatin-resistant cells also showed increased resistance to copper. In preoperative cervical cancer biopsy samples from poor prognoses patients after cisplatin chemoradiotherapy, FGF13-positive cells were detected more abundantly than in the biopsy samples from patients with good prognoses. These results suggest that FGF13 plays a pivotal role in mediating resistance to platinum drugs, possibly via a mechanism shared by platinum and copper. Our results point to FGF13 as a novel target and useful prognostic guide for cancer therapy.
Authors	Tomoko Okada, Kazuhiro Murata, Ryoma Hirose, Chie Matsuda, Tsunehiko Komatsu, Masahiko Ikekita, Miyako Nakawatari, Fumiaki Nakayama, Masaru Wakatsuki, Tatsuya Ohno, Shingo Kato, Takashi Imai, Toru Imamura
Journal	Scientific reports (Sci Rep) Vol. 3 Pg. 2899 (Oct 11 2013) ISSN: 2045-2322 [Electronic] England
PMID	24113164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents RNA, Messenger fibroblast growth factor 13 Fibroblast Growth Factors Cisplatin
Topics	Adult Alternative Splicing Antineoplastic Agents (pharmacology, therapeutic use) Cell Line, Tumor Cisplatin (pharmacology, therapeutic use) Drug Resistance, Neoplasm (genetics) Female Fibroblast Growth Factors (genetics) Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HeLa Cells Humans Middle Aged Neoplasm Staging RNA, Messenger (genetics, metabolism) Treatment Outcome Up-Regulation Uterine Cervical Neoplasms (drug therapy, genetics, mortality, pathology)

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