Oncogenic Role of Skp2 and p27Kip1 in Intraductal Proliferative Lesions of the Breast

ObjectiveTo investigate whether the connection of p27Kip1 to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.MethodsHere we investigated the mechanism involved in association of Skp2's degradation of p27Kip1 with the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27Kip1 protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH, n=30), atypical ductal hyperplasia (n=30), flat epithelial atypia (FEA, n=30), and ductal carcinoma in situ (DCIS, n=30). Moreover, the expression status of Skp2 and p27Kip1 in 30 cases of the normal breast paraffin-embedded tissues were explored.ResultsThe DCIS group was with the highest Skp2 level and the lowest p27Kip1 level, and the UDH group was with the lowest Skp2 level and the highest p27Kip1 level. Both Skp2 and p27Kip1 levels in the DCIS group were significantly different from those in the UDH group (all P<0.01). The levels of Skp2 and p27Kip1 in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05). p27Kip1 was negatively correlated with Skp2 in both the UDH group (r=-0.629, P=0.026) and DCIS group (r=-0.893, P=0.000).ConclusionOverexpression of Skp2 might be the mechanism underlying p27Kip1 over degradation.