Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.
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Primary tumor specimens were obtained between 1996 and 2010 from 181 cases of cervical cancer, 301 cases of high grade cervical intraepithelial neoplasia (CIN), and 99 cases of low grade CIN undergoing primary surgery at Gangnam Severance Hospital, Yonsei University College of Medicine. All patients gave oral and written informed consent. Paraffin blocks for some of the patients were provided by the Korea Gynecologic Cancer Bank through the Bio & Medical Technology Development Program of the Ministry of Education, Science, and Technology, Korea ( http://www.kgcb.or.kr ). All tumor tissues were histologically reviewed and only specimens with a sufficient abundance of tumor cells were included in tissue microarray construction. Staging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. Primary treatment for invasive cervical cancer consisted of a type 3 radical hysterectomy with pelvic lymph node dissection. Concurrent Platinum-based chemoradiation was given in cases with increased risk of recurrence, such as positive resection margins, positive lymph nodes, or parametrial invasion. Medical records were reviewed to obtain data including age, surgical procedure, survival time, and survival status. Response to therapy was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0), either by computed tomography or magnetic resonance imaging . Data on tumor size, cell type, tumor grade, and lymph node metastasis were obtained by reviewing pathology reports. The study protocol was approved by the Institutional Review Boards (IRBs) of Gangnam Severance Hospital and the Office of Human Subjects Research at the National Institutes of Health (NIH).
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