Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

AUTOR(ES)

Barbie, Thanh U.

FONTE

National Academy of Sciences

RESUMO

In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth of the C33A cervical cancer cell line by MIS is associated with induction of the p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer.

Documentos Relacionados

• Tissue-specific tumor suppressor activity of retinoblastoma gene homologs p107 and p130
• p130 and p107 use a conserved domain to inhibit cellular cyclin-dependent kinase activity.
• E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry.
• p130 Is Dispensable in Peripheral T Lymphocytes: Evidence for Functional Compensation by p107 and pRB
• RNA Polymerase III Transcription Factor IIIB Is a Target for Repression by Pocket Proteins p107 and p130