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Oncogenic Role of Skp2 and p27^(Kip1) in Intraductal Proliferative Lesions of the Breast 被引量:4

Oncogenic Role of Skp2 and p27^(Kip1) in Intraductal Proliferative Lesions of the Breast
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摘要 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. 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.
出处 《Chinese Medical Sciences Journal》 CAS CSCD 2012年第3期161-166,共6页 中国医学科学杂志(英文版)
基金 Supported by the National Natural Science Foundation of China(30471967) research funding of Tianjin Cancer Institute&Hospitalof Tianjin Medical University
关键词 SKP2 致癌作用 P27 增生性 乳腺癌 病变 管内 石蜡包埋组织 breast cancer intraductal proliferative lesions p27 ^Kip1 S-phase kinase-associated protein 2
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  • 1Clay CE, Namen AM, Atsumi G, Trimboli AJ, Fonteh AN, High KP, Chilton FH. Magnitude of peroxisome proliferator-activated receptor-gamma activation is associated with important and seemingly opposite biological responses in breast cancer cells. J Investig Med 2001; 49: 413-420.
  • 2Clay CE, Monjazeb A, Thorburn J, Chilton FH, High KP. 15-Deoxy-delta12,14-prostaglandin J2-induced apoptosis does not require PPARgamma in breast cancer cells. J Lipid Res 2002; 43: 1818-1828.
  • 3Place AE, Suh N, Williams CR, Risingsong R, Honda T, Honda Y, Gribble GW, Leesnitzer LM, Stimmel JB, Willson TM, Rosen E, Sporn MB. The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo. Clin Cancer Res 2003; 9: 2798-2806.
  • 4Wang M, Wise SC, Leff T, Su TZ. Troglitazone, an antidiabetic agent, inhibits cholesterol biosynthesis through a mechanism independent of peroxisome proliferator-activated receptor-gamma. Diabetes 1999; 48: 254-260.
  • 5Castrillo A, Mojena M, Hortelano S, Boscá L. Peroxisome proliferator-activated receptor-gamma-independent inhibition of macrophage activation by the non-thiazolidinedione agonist L-796,449. Comparison with the effects of 15-deoxy-delta(12,14)-prostaglandin J(2). J Biol Chem 2001; 276: 34082-34088.
  • 6Okano H, Shiraki K, Inoue H, Yamanaka Y, Kawakita T, Saitou Y, Yamaguchi Y, Enokimura N, Yamamoto N, Sugimoto K, Murata K, Nakano T. 15-deoxy-delta-12-14-PGJ2 regulates apoptosis induction and nuclear factor-kappaB activation via a peroxisome proliferator-activated receptor-gamma-independent mechanism in hepatocellular carcinoma. Lab Invest 2003; 83: 1529-1539.
  • 7Weber SM, Scarim AL, Corbett JA. PPARgamma is not required for the inhibitory actions of PGJ2 on cytokine signaling in pancreatic beta-cells. Am J Physiol Endocrinol Metab 2004; 286: E329-E336.
  • 8Shimada T, Kojima K, Yoshiura K, Hiraishi H, Terano A. Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells. Gut 2002; 50: 658-664.
  • 9Eibl G, Wente MN, Reber HA, Hines OJ. Peroxisome proliferator-activated receptor gamma induces pancreatic cancer cell apoptosis. Biochem Biophys Res Commun 2001; 287: 522-529.
  • 10Ohta K, Endo T, Haraguchi K, Hershman JM, Onaya T. Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells. J Clin Endocrinol Metab 2001; 86: 2170-2177.

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