The p53 family protein p73 encodes pro-apoptotic (TAp73) and anti-apoptotic (DNp73) isoforms. The functional role of the two isoforms in cancer development is still unclear. In this study, by yeast-2-hybrid screening using DNp73 as a bait, we identified C35 (C17orf37) as a novel protein interacting partner of p73. C35 was mapped to chromosome 17q12. It was overexpressed in breast cancer and prostate cancer. Its expression was positively correlated with the grade and stage of breast cancer progression. A recent study reported that C35 promotes cell migration and invasion in prostate cancer cells. However, the significance of C35 in cancer development remains to be elucidated. In this study, we focused on the functional role of C35 in gynaecological cancers. The binding of C35 and DNp73 was confirmed by co-immunoprecipitation. Quantitative real-time PCR revealed that mRNA expression of C35 in ovarian and cervical cancer cell lines was higher than that in normal cell lines. In addition, mRNA expression of C35 was significantly higher in ovarian cancer clinical samples than that in normal samples (p<0.0001, t-test). To investigate the function of C35, SiHa and OV2008 cells stably expressing C35 were established. The protein expression of C35 was confirmed by western blot analysis. In studying the effect of C35 on cell transforming ability, soft agar assay was performed. The result showed that the number of colonies formed by the C35 stable clones was significantly higher than those formed by the parental cells and control vector stably transfected cells. In addition, the size of the colonies formed by the C35 stable clones was larger. Wound healing assay and transwell migration assay were performed to investigate the effect of C35 on cell migration rate. We found that the migration rate of the C35 stable clones was higher than that of the parental cells and vector transfected cells. XTT assay revealed that the proliferation rate of the C35 stable clones was higher than that of the parental cells and vector controls. In summary, our findings suggested that C35 is overexpressed in ovarian cancer. C35 likely exerts its oncogenic roles to enhance transformation, cell migration and cell proliferation in gynaecological cancers. Further study of the significance of the DNp73-C35 interaction may give insight into their oncogenic properties.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1480.