Objective 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. Methods Here we investigated the me...Objective 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. Methods 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. Results 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). Conclusion Overexpression of Skp2 might be the mechanism underlying p27 Kip1 over degradation.展开更多
Objective:To observe the radiosensitivity effect of AG825 on breast cancer cell line with high expression of ERBB2 in vitro.Methods:MTT and clone formation assay were used to observe the effect of AG825 on proliferati...Objective:To observe the radiosensitivity effect of AG825 on breast cancer cell line with high expression of ERBB2 in vitro.Methods:MTT and clone formation assay were used to observe the effect of AG825 on proliferation and radiosensitivity of breast cancer line MDA-MB-453.After MDA-MB-453 was exposed to AG825 and radiation,comet assay and Western blotting were applied to detect double strand break and expressions DNA-PKcs protein,respectively.Results:AG825 inhibited proliferation rate and decrease survival fraction of MDA-MB-453.After radiation,compared with control group,expression of DNA-PKcs was lower in group with AG825 presence but double strand break was higher.Conclusion:AG825 could increase radiosensitivity of breast cancer cell line MDA-MB-453,and it may associate with its inhibition of radiation induced expression of DNA-PKcs and double strand break repair.展开更多
基金Supported by the National Natural Science Foundation of China(30471967)research funding of Tianjin Cancer Institute&Hospitalof Tianjin Medical University
文摘Objective 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. Methods 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. Results 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). Conclusion Overexpression of Skp2 might be the mechanism underlying p27 Kip1 over degradation.
基金a grant from the National Natural Science Foundation of China(No.30672426)
文摘Objective:To observe the radiosensitivity effect of AG825 on breast cancer cell line with high expression of ERBB2 in vitro.Methods:MTT and clone formation assay were used to observe the effect of AG825 on proliferation and radiosensitivity of breast cancer line MDA-MB-453.After MDA-MB-453 was exposed to AG825 and radiation,comet assay and Western blotting were applied to detect double strand break and expressions DNA-PKcs protein,respectively.Results:AG825 inhibited proliferation rate and decrease survival fraction of MDA-MB-453.After radiation,compared with control group,expression of DNA-PKcs was lower in group with AG825 presence but double strand break was higher.Conclusion:AG825 could increase radiosensitivity of breast cancer cell line MDA-MB-453,and it may associate with its inhibition of radiation induced expression of DNA-PKcs and double strand break repair.
