PPAR-γ和PTEN蛋白在膀胱移行细胞癌中的表达及意义
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摘要
目的测定膀胱移行细胞癌中PPAR-γ和PTEN蛋白的表达及与其病理分级、临床分期及预后相关性。方法免疫组织化学法检测PPAR-γ和PTEN于膀胱移行细胞癌标本及正常膀胱组织中的表达程度,病理分析仪测定蛋白表达程度。结果 (1)在正常膀胱组织中PPAR-γ蛋白的表达(20%)明显低于膀胱癌(68%),而正常膀胱组织PTEN蛋白的表达(100%)明显高于膀胱癌(52%),两者阳性率差异有统计学意义(P<0.05)。(2)膀胱移行细胞癌组织中PPAR-γ表达与临床分期、病理分期、淋巴结转移呈正相关性,PTEN蛋白表达呈负相关性。(3)PPAR-γ蛋白和PTEN蛋白在膀胱移行细胞癌中表达呈负相关关系(r=-0.604,P<0.05)。结论 PPAR-γ和PTEN可能参与了膀胱肿瘤的发生发展过程,对膀胱癌诊断、临床分期及预后有一定价值。
Objective To exolore the expression of ppar-gamma and PTEN in cell carcinoma of the bladder and the its correlation with pathologic grade,clinical stage and prognosis. Methods The expression of ppar-gamma and PTEN in bladder transitional cell carcinoma specimens and normal bladder tissues was detected by immunohistochemistry,and the expression level of protein was detected by pathological analyzer. Results(1) The expression of PPARgamma protein(20%) in normal bladder tissues was significantly lower than that of bladder cancer(68%),while the expression of PTEN protein in normal bladder tissues(100%) was significantly higher than that in bladder cancer(52%).The positive rate of the two markers had significant difference( P < 0. 01).(2) The expression of PPAR-gamma was positively correlated with clinical stage,pathological stage and lymph node metastasis in bladder transitional cell carcinoma,and negatively correlated with PTEN protein expression.(3)There was a negative correlation between PPAR-gamma protein and PTEN protein in bladder transitional cell carcinoma( r =-0. 604,P < 0. 05). Conclusion Ppar-gamma and PTEN may be involved the occurrence and development of bladder cancer and maybe has some value in clinical diagnosis,staging and prognosis judgment of bladder cancer.
Objective To exolore the expression of ppar-gamma and PTEN in cell carcinoma of the bladder and the its correlation with pathologic grade,clinical stage and prognosis. Methods The expression of ppar-gamma and PTEN in bladder transitional cell carcinoma specimens and normal bladder tissues was detected by immunohistochemistry,and the expression level of protein was detected by pathological analyzer. Results(1) The expression of PPARgamma protein(20%) in normal bladder tissues was significantly lower than that of bladder cancer(68%),while the expression of PTEN protein in normal bladder tissues(100%) was significantly higher than that in bladder cancer(52%).The positive rate of the two markers had significant difference( P < 0. 01).(2) The expression of PPAR-gamma was positively correlated with clinical stage,pathological stage and lymph node metastasis in bladder transitional cell carcinoma,and negatively correlated with PTEN protein expression.(3)There was a negative correlation between PPAR-gamma protein and PTEN protein in bladder transitional cell carcinoma( r =-0. 604,P < 0. 05). Conclusion Ppar-gamma and PTEN may be involved the occurrence and development of bladder cancer and maybe has some value in clinical diagnosis,staging and prognosis judgment of bladder cancer.
引文
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[11]YU J,SHEN B,CHU ES,et al.Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro[J].Hepatology,2010,51(6):2008-2019.
[12]TAN X,DAGHER H,HUTTON CA,et a1.Effects of PPAR gamma ligands on TGF-beta1-induced epithelialmesenchymal transition in alveolar epithelial cells[J].Respir Res,2010,11(1):21.
[13]PRINGLE DR,VASKO VV,MANCHANDA PK,et al.Follicular thyroid cancers demonstrate dual activation of PKA and m TOR as modeled by thyroid specific deletion of Prkar1a and Pten in mice[J].J Clin Endocrinol Metab,2012,99(5):E804-E812.
[14]SUN C,ZHAO J,JIN Y,et al.PTEN regulation of the proliferation and differentiation of auditory progenitors through the PTEN/PI3K/Akt-signaling pathway in mice[J].Neuroreport,2011,25(3):177-183.
[15]DILLON LM,MILLER TW.Therapeutic targeting of cancers with loss of PTEN function[J].Curr Drug Targets,2012,15(1):65-79.
[16]张萌,彭利,乔治斌,等.罗格列酮通过PI3K/PTEN/Akt通路抑制人肝癌Hep G2细胞增殖[J].细胞与分子免疫学杂志,2014,30(2):147-150.
[17]LANGLE Y,LODILLINSKY C,BELGOROSKY D,et al.Role of peroxisome proliferator activated receptor-gamma in bacillus Calmette-Guérin bladder cancer therapy[J].J Urol,2012,188(6):2384-2390.
[2]MATSUDA S,KITAGISHI Y.Peroxisome proliferator-activated receptor and vitamin d receptor signaling pathways in cancer cells[J].Cancers(Basel),2013,5(4):1261-1270.
[3]KAKEHASHI A,HAGIWARA A,IMAI N,et al.Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat:evidence for a role of oxidative stress via activation of CAR,PXR and PPAR signaling pathways[J].Toxicol Appl Pharmacol,2013,273(2):390-400.
[4]MANDARD S,PATSOURIS D.Nuclear control of the inflammatory response in mammals by peroxisome proliferator-activated receptors[J].PPAR Res,2013(36):613864.
[5]SAWAYAMA H,ISHIMOTO T,WATANABE M,et al.Small molecule agonists of PPAR-γexert therapeutic effects in esophageal cancer[J].Cancer Res,2010,74(2):575-585.
[6]NAGUIB A,COOKE JC,HAPPERFIELD L,et al.Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study:associations with clinicopathological and dietary factors[J].BMC Cancer,2011,11(1):1-11.
[7]WANG X,SUN Y,WONG J,et al.PPARγmaintains ERBB2-positive breast cancer stem cells[J].Oncogene,2013,32(49):5512-5521.
[8]PARK JH,HAN SW,OH DY,et al.Analysis of KRAS,BRAF,PTEN,IGF1R,EGFR intron 1 CA status in both primary tumors and paired metastases in determining benefit from cetuximab therapy in colon cancer[J].Cancer Chemoth Pharm,2011,68(4):1045-1055.
[9]LUBET RA,FISCHER SM,STEELE VE,et al.Rosiglitazone,a PPAR gamma agonist:potentpromoter of hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers[J].Int J Cancer,2008,123(10):2254-2259.
[10]BABJUK M,OOSTERLINCK W,SYLVESTER R,et al.EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder,the 2011 update[J].Eur Urol,2011,59(6):997-1008.
[11]YU J,SHEN B,CHU ES,et al.Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro[J].Hepatology,2010,51(6):2008-2019.
[12]TAN X,DAGHER H,HUTTON CA,et a1.Effects of PPAR gamma ligands on TGF-beta1-induced epithelialmesenchymal transition in alveolar epithelial cells[J].Respir Res,2010,11(1):21.
[13]PRINGLE DR,VASKO VV,MANCHANDA PK,et al.Follicular thyroid cancers demonstrate dual activation of PKA and m TOR as modeled by thyroid specific deletion of Prkar1a and Pten in mice[J].J Clin Endocrinol Metab,2012,99(5):E804-E812.
[14]SUN C,ZHAO J,JIN Y,et al.PTEN regulation of the proliferation and differentiation of auditory progenitors through the PTEN/PI3K/Akt-signaling pathway in mice[J].Neuroreport,2011,25(3):177-183.
[15]DILLON LM,MILLER TW.Therapeutic targeting of cancers with loss of PTEN function[J].Curr Drug Targets,2012,15(1):65-79.
[16]张萌,彭利,乔治斌,等.罗格列酮通过PI3K/PTEN/Akt通路抑制人肝癌Hep G2细胞增殖[J].细胞与分子免疫学杂志,2014,30(2):147-150.
[17]LANGLE Y,LODILLINSKY C,BELGOROSKY D,et al.Role of peroxisome proliferator activated receptor-gamma in bacillus Calmette-Guérin bladder cancer therapy[J].J Urol,2012,188(6):2384-2390.