title: CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis.
abstract: CIP2A is a recently characterized oncoprotein which involves in the progression of several human malignancies. This study aimed to investigate its clinical significance and biological function in ovarian cancer. CIP2A expression was analyzed in 152 archived ovarian cancer specimens using immunohistochemistry. One hundred cases (65.79 %) showed CIP2A overexpression, including 63 of 92 serous carcinomas (68.48 %), 21 of 33 endometrioid carcinomas (63.64 %), 12 of 23 mucinous carcinomas (52.17 %), and 4 of 4 clear cell carcinomas (100 %). There is no significant difference of CIP2A expression between serous tumors and all other morphologies combined. CIP2A overexpression positively correlated with advanced FIGO stage (p = 0.0336) and tumor grade (p = 0.0213). siRNA knockdown was performed in A2780 and SKOV3 cell lines. MTT, colony formation assay, and flow cytometry were carried out to assess the role of CIP2A in proliferation, cell cycle, and apoptosis. CIP2A depletion in ovarian cancer cell lines inhibited proliferation, blocked cell cycle progression, and increased paclitaxel-induced apoptosis. Furthermore, CIP2A depletion downregulated cyclin D1, c-myc, phospho-Rb, Bcl-2, and phospho-AKT expression. These results validate the role of CIP2A as a clinically relevant oncoprotein and establish CIP2A as a promising therapeutic target of ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, 110004 Shenyang, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Li
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Wang
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D001324:Autoantigens / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger