Journal Article

An integrative functional genomic and gene expression approach revealed SORBS2 as a putative tumour suppressor gene involved in cervical carcinogenesis

Claudia Backsch, Bettina Rudolph, Daniel Steinbach, Cornelia Scheungraber, Melanie Liesenfeld, Norman Häfner, Markus Hildner, Andreas Habenicht, Ingo B. Runnebaum and Matthias Dürst

in Carcinogenesis

Volume 32, issue 7, pages 1100-1106
Published in print July 2011 | ISSN: 0143-3334
Published online May 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr093
An integrative functional genomic and gene expression approach revealed SORBS2 as a putative tumour suppressor gene involved in cervical carcinogenesis

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Human papillomavirus (HPV) types 16 and 18 are known to play a major role in cervical carcinogenesis. However, additional genetic alterations are required for the development and progression of cervical cancer. Our aim was to identify genes which are consistently down-regulated in cervical cancers (CxCa) and which are likely to contribute to malignant transformation. Microarray analyses of RNA from high-grade cervical precancers (CIN2/3) and CxCa were performed to screen for putative tumour suppressor genes (TSG) in predefined regions on chromosomes 4 and 10. Validation of the candidate genes was done by quantitative reverse transcription–polymerase chain reaction (qRT–PCR) in 16 normal cervical tissues, 14 CIN2/3 and 16 CxCa. The two most promising genes, SORBS2 and CALML5, were expressed ectopically in various cell lines in order to analyse their functional activity. Reconstitution of SORBS2 expression resulted in a significant reduction in cell proliferation, colony formation and anchorage-independent growth in CaSki, HPKII and HaCaT cells, whereby anchorage-independent growth could only be investigated for CaSki cells. SORBS2 had no effect on cell migration. In contrast, reconstitution of CALML5 expression did not influence the phenotype of all cell lines tested. None of the genes could induce senescence or apoptosis. Our results underline a possible role of SORBS2 as a TSG in cervical carcinogenesis.

Journal Article.  5314 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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