Abstract P4-05-11: CENPU acts as a new proto-oncogene to regulate tumorigenesis and cancer metastasis in breast cancer

Abstract

Abstract Background: Centromere protein (CENPU) gene locus is at chromosome 4q35.1, encoding a protein with some classic functional domains; recently some research groups proved CENPU protein is a constitutive kinetochore component and regulates cell-cycle status by recruitment of function-specific proteins. Homologous gene in murine hematopoiesis system represents early erythroblasts-specific expression. Our previous research had found that about 25 % of transgenic mice amplified CENPU would suffer breast cancer in body surface which induce us to hypothesize that CENPU gene and its protein played an important role in breast cancer occurrence and development. Methods: CENPU protein expression was examined in normal mammary tissue, DCIS tissue, primary invasive breast cancer and different human breast cancer cell lines. Cell type and epitope-dependent subcellular-specific CENPU staining pattern in normal mammary gland epithelium and cancer biopsies were correlated to molecular and clinical parameters. A CENPU-specific small inhibitory RNA (siRNA) was introduced into MDA-MB-231 human breast cancer cell lines to investigate its effect on cancer cell growth, migration and invasion. Distribution of cell cycles were examined with flow cytometry. Test the tumorigenicities of si-control and si-CENPU cells by soft agar colony formation assay. Migration was observed by wound healing and transwell migration assays. The expression of related pathway proteins were determined by Western blotting analysis. Results: Compared with normal mammary and DCIS tissues, CENPU protein was highest expression in primary invasive breast cancer tissue (P<0.001).Then we compared CENPU expression lever between no metastasis and metastasis patients during three year, and found that CENPU expression in recurrence group is higher than no-metastasis group (P<0.01). CENPU protein expression of different human breast cancer cell lines were detected, which found the CENPU in triple negative breast cancer cell line, MDA-MB-231, was the highest expression. Knockdown of CENPU by specific siRNA in MDA-MB-231 reduced the ability of colony formation and induced the G2/M phase arrest. Moreover, the migration rate of si-CENPU MDA-MB-231 cancer cells was significantly reduced as compared with si-controls (P<0.01).With the knockdown of CENPU, the E-cadherin expression was up-regulated and the N-cadherin, AKT1 and NF-κB were downp-regulated. Conclusion: We propose that CENPU functions as a novel proto-oncogene to regulate oncogenesis and metastasis. In further, in vivo study is needed to evaluate the biologaical importance of CENPU in breast cancer. Citation Format: Jin Zhang, Xiaobei Zhang, Yunhui Hu, Jiao Li, Jingjing Liu, Sheng Zhang, Wei Su. CENPU acts as a new proto-oncogene to regulate tumorigenesis and cancer metastasis in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-11.