title: SOX9, a potential tumor suppressor in cervical cancer, transactivates p21WAF1/CIP1 and suppresses cervical tumor growth.
abstract: Sex-determining region Y-box 9 protein (SOX9) is a transcription factor that may act as both oncogene and tumor suppressor depending on tumor origin. Here we found that SOX9 expression was progressively decreased in cervical carcinoma in situ and especially in invasive cervical carcinoma, compared with normal cervix tissue. The effects of SOX9 on the proliferation, viability, and tumor formation of cervical carcinoma cells were assessed through the silencing and overexpression of SOX9. Overexpression of SOX9 in cervical carcinoma cells (SiHa and C33A) inhibited cell growth in vitro and tumor formation in vivo. In agreement, the silencing of SOX9 in HeLa cells promoted cell growth in culture and tumor formation in mice. Overexpression of SOX9 transactivated p21WAF1/CIP1 via a specific promoter region, thus blocking G1/S transition. The quantitative chromatin immunoprecipitation analysis revealed physical interaction between SOX9 and the specific region of the p21WAF1/CIP1 promoter. We suggest that SOX9 is a potential therapeutic target in cervical carcinoma, that specifically transactivates p21WAF1/CIP1.
authors.affiliation: Department of Reproductive Medicine, The First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Reproductive Medicine, The First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lian
authors.affiliation: Department of Reproductive Medicine, The First Affiliated Hospital, Xi'an Jiaotong University Medical School, Xi'an, China.
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009857:Oncogenes; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: SOX9; cervical carcinoma; oncogene; p21WAF1/CIP1; tumor suppressor