title: Identification of the deleted in split hand/split foot 1 protein as a novel biomarker for human cervical cancer.
abstract: The morphological detection of early neoplastic transformation leading to cervical cancer remains problematic. In this work, we have identified deleted in split hand/split foot 1 protein (DSS1) as an early biomarker that is specifically upregulated in premalignant and malignant cervical epithelial cells, but is low or undetectable in non-malignant cells. DSS1 mRNA and protein levels are significantly increased in cultured human cervical carcinoma cell lines originating from primary and metastatic tumors. In fact,  > 96% of patient tumor tissues were found to have cells with elevated DSS1 when compared with tumor-adjacent normal cells. In histological sections of cervical tissue containing either invasive cervical carcinoma or its precursor lesions, DSS1 was readily detected in the tumor cells. Steady-state DSS1 expression by immortalized cervical cancer cell lines was found to be necessary for maintenance of their transformed phenotype, since stable shRNA-mediated depletion of DSS1 in HeLa cells inhibited their proliferation and colony-forming activity in monolayer cultures and prevented division of these cells in soft agar. When DSS1 levels are reduced using shRNA, the cells ultimately undergo apoptosis via activation of p53 and the p53 downstream targets, and cleavage of apoptosis-associated proteins including CPP32/caspase-3, poly(ADP-ribose)polymerase and DNA-PKcs. In addition, silencing of DSS1 makes cervical cancer cells sensitive to cell death after treatment with cisplatin. We conclude that the DSS1 protein is critically involved in the maintenance of the transformed phenotype in cervical cancer cells, and that it might be a specific, robust and reliable marker for early detection, diagnosis and treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine,  Kaohsiung, Taiwan.
authors.forename: Yen-Ying
authors.initials: YY
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Fang-Mei
authors.initials: FM
authors.lastname: Chang
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.forename: Tiffany
authors.initials: T
authors.lastname: Trieu
authors.forename: Hannah I
authors.initials: HI
authors.lastname: Pridgen
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Huang
authors.forename: Karina
authors.initials: K
authors.lastname: Patiño-Guzman
authors.forename: Nabih
authors.initials: N
authors.lastname: Diab
authors.forename: Angelica
authors.initials: A
authors.lastname: Cantu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Slaga
authors.forename: Sung-Jen
authors.initials: SJ
authors.lastname: Wei
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D012333:RNA, Messenger; C484606:SEM1 protein, human; D046988:Proteasome Endopeptidase Complex