10609 Background: Skp2 (S-phase kinase-associated protein 2) is substrate-recognizing subunit of an ubiquitin E3 ligase SCF (Skp1, Cullin and F-box) complex and has a major role in p27 regulation. Overexpression of Skp2 is frequently seen in human tumors, often correlating with poor prognosis. Anaphase-promoting complex/cyclosome (APC/C) is another most prominent ubiquitin E3 ligase in cell cycle control, and its function is tightly controlled by activating subunit Cdh1 (Fizzy-related). APC-Cdh1 complex is supposed to be involved in Skp2 proteolysis and have essential role for S phase entry, however clinical significance of Cdh1 have not evaluated yet. Herein we examined the significance of Cdh1 in breast cancer. Methods: Firstly, MCF7 human breast cancer cells and MCF10A normal breast epithelial cells were analyzed in vitro and in vivo. Thereafter, using tissue microarray, we evaluate the expression profile of Cdh1, Skp2 and p27 in both breast cancer and normal breast epithelial tissue. Moreover, clinicopathological significance (age, tumor size, lymph node metastasis, distant metastasis, histological grade, and stage) of Cdh1 was analyzed from 126 breast cancer patients. Chi square-test, Fisher's exact test were used for statistical analysis of immunostaining results and clinicopathological data. p<0.05 was considered statistically significant. Results: Overexpression of Cdh1 induced attenuation of Skp2 and increased p27 protein expression, resulted in growth suppression. Moreover, knockdown of Cdh1 promoted higher Skp2 expression and S-phase population, reduced p27 and consequently induced cell transformation and proliferation in vitro and in vivo. Tissue microarray results appeared that positive Cdh1 and p27 was more frequently seen in normal breast tissue and statistically significant. On the other hand, Skp2 was less in normal tissue. Furthermore, Cdh1 positive breast cancer was more frequently seen in low histological grade tumors and statistically significant (p=0.04). Conclusions: Skp2 protein expression is regulated by Cdh1 in breast cancer. Cdh1 expression could be possible novel biomarker in patient with breast cancer. No significant financial relationships to disclose.