Oncogenic role of Skp2 and p27Kip1 in intraductal proliferative lesions of the breast / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether the connection of p27(Kip1) to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.</p><p><b>METHODS</b>Here we investigated the mechanism involved in association of Skp2’s degradation of p27(Kip1) with the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27(Kip1) 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 p27(Kip1) in 30 cases of the normal breast paraffin-embedded tissues were explored.</p><p><b>RESULTS</b>The DCIS group was with the highest Skp2 level and the lowest p27(Kip1) level, and the UDH group was with the lowest Skp2 level and the highest p27(Kip1) level.Both Skp2 and p27(Kip1) levels in the DCIS group were significantly different from those in the UDH group (all P<0.01).The levels of Skp2 and p27(Kip1) in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05).p27(Kip1) 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).</p><p><b>CONCLUSION</b>Overexpression of Skp2 might be the mechanism underlying p27(Kip1) over degradation.</p>

[Expression of alpha-tubulin and gamma-tubulin in premalignant lesion and carcinoma of breast and the significance thereof].

OBJECTIVE: To investigate the expression of alpha-tubulin and gamma-tubulin, 2 kinds of centrosome proteins, in premalignant lesion and carcinoma of breast and the significance thereof. METHODS: Forty specimens of premalignant lesions of breast, 40 specimens of infiltrating ductal carcinoma of breast, 40 specimens of intraductal carcinoma (IDC), and 30 specimens of normal breast tissues were obtained during operation. Immunohistochemistry was used to analyze the protein expression of alpha-tubulin and gamma-tubulin, and the percentages of ki67 positive cells. Western blotting was used to examine the mRNA expression of alpha-tubulin and gamma-tubulin. RESULTS: The protein and mRNA expression values of alpha-tubulin and gamma-tubulin in breast carcinoma were higher than those in the premalignant lesions and normal breast tissues with significant differences between the premalignant lesions and normal breast torques and without significant differences between infiltrating ductal carcinoma of breast and IDC. The ki67 positive rates of the infiltrating ductal carcinoma of breast group, IDC group, premalignant lesion group, and normal breast tissues group were 16.0%, 37.0%, 53.6%, and 67.8% (P = 0.001). A positive correlation existed between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P = 0.00) and there was no significant correlation between the expression of alpha-tubulin and the expression of gamma-tubulin in the same case and the same group (all P > 0.05). Both the expression of alpha-tubulin and the expression of gamma-tubulin were significantly associated with the prognosis. CONCLUSIONS: Centrosome protein is one of the distinct phenotypes of breast cancer cells. Aberration of centrosome proteins may be used to screen high risk cases of breast carcinoma and to estimate the prognosis.