Frequent alterations of the beta-catenin protein in cancer of the uterine cervix.
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. Beta-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 beta-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 beta-catenin protein in tumors from the uterine cervix and cell lines derived from them. Beta-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 beta-catenin gene. Our findings indicate that alterations of beta-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.
Pereira-Suárez
Ana Laura
AL
Departmento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas - UNAM, México DF, México.
Meraz
Marco Antonio
MA
Lizano
Marcela
M
Estrada-Chávez
Ciro
C
Hernández
Fernando
F
Olivera
Primitivo
P
Pérez
Elizabeth
E
Padilla
Patricia
P
Yaniv
Moshe
M
Thierry
Françoise
F
García-Carrancá
Alejandro
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin