Abstract
Human papillomavirus (HPV) plays a crucial role in cervical cancer etiology. However, not all HPV-infected women develop cancer, indicating that additional cellular factors facilitate carcinogenesis. The aim of this study was to analyze the expression profile of insulin-like growth factor 1 (IGF1) isoforms in the context of FOX2, SP1 and IGF1 receptor (IGF1R) expression during HPV-dependent cervical carcinogenesis. One hundred and nine epithelial tissue samples from women with pre-cancerous and cancer lesions of the cervix were analyzed. HPV DNA was identified by PCR, and real-time PCR was used to quantify the expression levels of the analyzed genes. All IGF1 mRNA splicing isoforms were up-regulated in pre-cancerous cells, and a shift in the balance towards mitogenic IGF1Eb was observed in the cancer samples. IGF1 expression was controlled mainly by the P1 promoter, and an increase in P2 usage was observed in the cancer. Correlations between IGF1 mRNA splicing isoforms and the FOX2 splicing factor, as well as P1/P2 activity and SP1 transcription factor expression levels were detected. No correlation was observed between the expression of IGF1 and its receptor IGF1R. Our results suggest that IGF1, in particular its splicing profile, may be an additional prognostic factor in cervical carcinogenesis.
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