title: Expression and prognostic role of SKIP in human breast carcinoma.
abstract: Ski-interacting protein (SKIP) is a nuclear hormone receptor-interacting cofactor, interactions with the proto-oncogene Ski, appears to modulate a number of signalling pathways involved in control of cell proliferation and differentiation, and may play a critical role in oncogenesis. In the present study, to investigate the potential roles of SKIP in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SKIP and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SKIP in 85 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. We found that SKIP was over expressed in breast carcinoma as compared with the adjacent normal tissues. High expression of SKIP was positively associated with histological grade (P = 0.01) and Ki-67 (P = 0.004). Univariate analysis showed that SKIP expression was associated with a poor prognosis (P = 0.006). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated. In addition, we employed small interfering RNA (siRNA) technique to knock down SKIP expression and observed it effects on MDA-MB-231 cells growth. SKIP depletion by siRNA inhibited cell proliferation, blocked S phase and decreased cyclin A and cyclin B levels. On the basis of these results, we suggested that SKIP overexpression was involved in the pathogenesis of breast cancer, which might serve as a future target for breast cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China, liuxiaobing0814@sina.com.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Liu
authors.forename: Qichao
authors.initials: Q
authors.lastname: Ni
authors.forename: Junfei
authors.initials: J
authors.lastname: Xu
authors.forename: Chenyi
authors.initials: C
authors.lastname: Sheng
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Chen
authors.forename: Shuyun
authors.initials: S
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D061986:MCF-7 Cells; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019394:Ki-67 Antigen; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C466999:SPHKAP protein, human