Frequent Alterations of the β-Catenin Protein in Cancer of the Uterine Cervix

Abstract

Cancer of the uterine cervix is still the leading cause of death among women with cancer in developing countries. Although infections with human papillomavirus are necessary, other molecular alterations that are needed at the cellular level for development of these tumors remain largely unknown. β-Catenin is a key regulator located within the Wnt signaling cascade whose alterations constitute an important event in colon carcinogenesis. In many malignancies increased levels of the β-catenin protein have been found, associated with its nuclear and/or cytoplasmic accumulation. To search for possible alterations of this pathway we examined the expression and localization of the β-catenin protein in tumors from the uterine cervix and cell lines derived from them. β-Catenin was found accumulated in the cytoplasm and/or nuclei of 12 out of 32 samples. In accordance, increased levels of this protein were observed in 9 out of 20 tumors analyzed. Importantly, PCR-SSCP and sequence analysis showed no mutations in exons 3, 4 and 6 of the β-catenin gene. Our findings indicate that alterations of β-catenin are frequent in these tumors and suggest that they may play an important role in the development of cancer of the uterine cervix. They also indicate that higher protein levels and abnormal localization may result from several different mechanisms.