Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
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A-Ram Kang1, Hyoung-Tae An1, Jesang Ko1, Eui-Ju Choi1 and Seongman Kang1
1Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
Seongman Kang, email: email@example.com
Keywords: ATXN1, cervical cancer, EGFR–RAS–MAPK pathway, tumorigenesis
Received: June 14, 2017 Accepted: September 20, 2017 Published: October 10, 2017
Ataxin-1 (ATXN1) is a coregulator protein within which expansion of the polyglutamine tract causes spinocerebellar ataxia type 1, an autosomal dominant neurodegenerative disorder. Previously, we reported that ATXN1 regulates the epithelial–mesenchymal transition of cervical cancer cells. In the present study, we demonstrate that ATXN1 is involved in cervical cancer tumorigenesis by promoting the proliferation of human cervical cancer cells. Chromatin immunoprecipitation assays showed that ATXN1 bound to the promoter region within cyclin D1 and activated cyclin D1 transcription, resulting in cell proliferation. ATXN1 promoted cyclin D1 expression through the EGFR–RAS–MAPK signaling pathway. Mouse xenograft tumorigenicity assays showed that ATXN1 downregulation inhibited tumorigenesis in cervical cancer cell lines in nude mice. Human cervical cancer tissue microarrays and immunohistochemical techniques showed that ATXN1 was significantly upregulated in many such tissues. Our results suggest that ATXN1 plays an important role in cervical cancer tumorigenesis and is a prognostic marker for cervical cancer.
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