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前列腺癌中RhoC和Rho激酶1的表达及其对丝裂原活化蛋白激酶和Akt蛋白的影响 被引量:11

Expression of RhoC and ROCK-1 and their effects on MAPK and Akt proteins in prostate carcinoma
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摘要 目的检测RhoC和Rho激酶1(ROCK-1)在前列腺癌中的表达,探讨RhoC和ROCK-1在前列腺癌形成过程中的可能作用。方法收集73例前列腺癌患者穿刺活检或手术切除的癌组织和对应的癌旁组织。采用逆转录聚合酶链反应(RT—PCR)检测RhoC mRNA和ROCK-1 mRNA表达,采用Western blot和免疫组化法检测RhoC和ROCK-1蛋白的表达。构建RhoC基因真核表达载体,转染前列腺癌不转移亚系PC-3M-284,并检测丝裂原活化蛋白激酶(MAPK)和Akt磷酸化水平变化。结果前列腺癌组织中,RhoC mRNA和ROCK-1 mRNA的阳性率分别为72.6%(53/73)和68.5%(50/73),癌旁组织分别为34.2%(25/73)和38.4%(28/73),差异均有统计学意义(均P〈0.01)。RhoC mRNA和ROCK-1 mRNA的表达与肿瘤转移呈正相关,而与肿瘤的Gleason分级无关。RhoC和ROCK-1蛋白在前列腺癌组织中的表达高于癌旁组织,并且与磷酸化MAPK和磷酸化Akt的表达呈正相关。携带RhoC基因的载体转染PC-3M-284细胞后,可以上调MAPK和Akt的磷酸化表达水平。结论RhoC和ROCK一1在前列腺癌组织中的表达高于癌旁组织,且与肿瘤转移相关。RhoC和ROCK一1可能通过活化MAPK和Akt参与了前列腺癌的形成、浸润和转移。 Objective To detect the expression of RhoC and Rho kinase 1 (ROCK-1) in prostate carcinoma, and explore the possible mechanism of RhoC/ROCK-1 in the pathogenesis of prostate carcinoma. Methods Tissue specimens from 73 patients with prostate carcinoma and corresponding paracancerous tissues were obtained by prostate cancer biopsy or radical prostatectomy. The expression of RhoC/ROCK-1 mRNA was detected by RT-PCR. Western blot and immunohistochemistry were performed to derteet the expression of RhoC/ROCK-1 protein. Eukaryotic expression plasmids of RhoC were constructed and transfected into PC-3M-21M cells, p-MAPK and p-Akt were detected by Western bolt. Results The expression levels of RhoC and ROCK-1 mRNA in the prostate carcinomas were significantly higher than those in corresponding paracancerous tissues [72.6% (53/73) vs. 34.2% (25/73) ;68.5% (50/73)vs. 38.4% (28/73), P 〈0.01 ], respectively. The results indicated that RhoC/ROCK-1 mRNA expression had no significant correlation with Gleason grade. However, the expression of RhoC/ROCK-1 mRNA showed a significant positive correlation with distant metastasis. The RhoC/ROCK-1 protein expression in prostate cancer was also higher than corresponding paracancerous tissues, and showed a significant positive correlation with p-MAPK and p-Akt expression levels. In addition, p-MAPK and p-Akt expression levels were up-regulated in the transcripts. Conclusion Expression levels of RhoC and ROCK-1 in prostate carcinoma are higher than those in corresponding paracaneerous tissues, showing a significant positive correlation with distant metastasis. RhoC/ROCK-1 may be involved in the development, invasion and metastasis of prostate carcinoma.
出处 《中华肿瘤杂志》 CAS CSCD 北大核心 2011年第3期202-206,共5页 Chinese Journal of Oncology
基金 江苏省卫生厅资助项目(P200956)
关键词 前列腺肿瘤 RHOC Rho激酶1 丝裂原活化蛋白激酶 AKT 浸润 转移 Prostatic neoplasms RhoC Rho kinase 1 Mitogen-activated protein kinase Akt Invasion Metastasis
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参考文献13

  • 1Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin, 2008, 58:71-96.
  • 2那彦群,李鸣.重视前列腺癌诊治规范化研究[J].中华医学杂志,2005,85(45):3169-3169. 被引量:21
  • 3叶洁梅,周洁,冷静.瘦素与前列腺癌[J].基础医学与临床,2008,28(7):778-780. 被引量:4
  • 4Ridley A. Molecular switches in metastasis. Nature, 2000, 6: 466-467.
  • 5Jaffe AB, Hall A. Rho GTPases : biochemistry and biology. Annu Rev Cell Dev Biol, 2005, 21:247-269.
  • 6Malliri A, Collard JG. Role of Rho-family proteins in cell adhesion and cancer. Curr Opin Cell Biol, 2003, 5:583-589.
  • 7Wheeler AP, Ridley AJ. Why three Rho proteins.9 RhoA, RhoB, RhoC, and cell motility. Exp Cell Res, 2004, 301:43-49.
  • 8Clark EA, Golub TR, Lander ES, et al. Genomic analysis of metastasis reveals an essential role for RhoC. Nature, 2000, 406 : 532-535.
  • 9van Golen KL, Bao L, DiVito MM, et al. Reversion of RhoC GTPaseinduced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Mol Cancer Ther, 2002, 1 : 575- 583.
  • 10Yao H, Dashner EJ, van Golen CM, et al. RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility. Oncogene, 2006, 25:2285-2296.

二级参考文献13

  • 1王辉,肖新华,鄢盛凯,孙琦,王姮.2型糖尿病患者血清脂联素、瘦素和游离脂肪酸与代谢及炎症因子的相关性[J].基础医学与临床,2006,26(5):503-507. 被引量:13
  • 2Calle EE, Rodriguez C, Walker-Thurmond K, et al. Obesity, and mortality from cancer in a prospectively studied cohort of US adults[J]. N Engl J Med,2003,348:1625 - 1638.
  • 3Frankenberry KA, Somasundar P, McFadden DW, et al.Leptin induces cell migration and the expression of growth factors in human prostate cancer cells[J]. Am J Surg,2004, 188:560 - 565.
  • 4Onuma M, Bub JD, Rummel TD, et al. Prostate cancer cell-adipocyte interaction: leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase[ J]. J Biol Chem,2003 ,278 :42660 -42667.
  • 5Baillargeon J, Rose D. Obesity, adipokines and prostate cancer [ J ]. J Oncol,2006,28 (3) :737 - 745.
  • 6Cascio S, Bartella V, Auriemma A, et al. Mechanism of leptin expression in breast cancer cells : role of hypoxia-inducible factor-1 alpha [ J ]. Oncogene, 2008,27:540 - 548.
  • 7Saxena NK, Vertino PM, Anania FA, et al. Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3 [ J ]. J Biol Chem,2007,282 (18) :13316 - 13325.
  • 8Chen Chiachen, Chang YuanChing, Liu Chienliang, et al. Leptin induces proliferation and anti-apoptosis in human hepatocarcinoma cells by up-regulating cyclin D1 and down-regulating Bax via a Janus kinase 2-linked pathway [ J ]. Endocr Relat Cancer, 2007,14 (2) : 513 - 529.
  • 9Ogunwobi OO, Beales IL. Cyclo-oxygenase-independent inhibition of apoptosis and stimulation of proliferation by leptin in human colon cancer cells [ J ]. Dig Dis Sci, 2007,52 (8) :1934 -1945.
  • 10Hoda MR, Keely SJ, Bertelsen LS,et al. Leptin acts as a mitogenic and antiapoptotic factor for colonic cancer cells [ J ]. British Journal Surg Society, 2007,94 ( 3 ) : 346 - 354.

共引文献23

同被引文献60

  • 1Xiao-Xia Wang,Xiao-Zhong Li,Li-Qin Zhai,Zhi-Rong Liu,Xian-Jiu Chen,Yi Pei.Overexpression of IQGAP1 in human pancreatic cancer[J].Hepatobiliary & Pancreatic Diseases International,2013,12(5):540-545. 被引量:3
  • 2邱兴烽,王效民,殷平.RhoC与恶性肿瘤的侵袭转移[J].国外医学(生理病理科学与临床分册),2005,25(2):136-139. 被引量:4
  • 3陈明流,石铮.RhoC基因与肿瘤的侵袭和转移[J].医学综述,2005,11(11):995-997. 被引量:3
  • 4王德盛,晋亮,孙辰婧,窦科峰.Rho蛋白在肿瘤发生发展中的作用[J].国际肿瘤学杂志,2006,33(12):887-890. 被引量:2
  • 5卢希,韩昱晨.Rho蛋白在肿瘤的侵袭、转移中的作用[J].实用肿瘤学杂志,2007,21(3):296-298. 被引量:6
  • 6Narumiya S,Tanji M, Ishizaki T. Rho signaling, ROCK and mDial,in transformation, metastasis and invasion [ J ]. Cancer and Metastasis Rev,2009,28( 1 -2) :65 -76.
  • 7Hahmann C, Schroeter T. Rho-kinase inhibitors as therapeutics : from pan inhibition to isoform selectivity [ J ]. Cell Mol Life Sci,2010,67 (2) :171 -177.
  • 8Liu S. The ROCK signaling and breast cancer metastasis [ J ]. Mol Bio Rep,2011,38(2) :1363 - 1366.
  • 9Riento K, Ridley AJ. ROCKs: multifunctional kinases in cell behav- iour[ J]. Nat Rev Mol Cell Biol,2003,4(6) :446 -456.
  • 10Denker SP, Huang DC, Orlowski J, et al. Direct binding of the Na-H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell Shape independently of H( + )translocation[ J]. Mol Cell, 2000,6 (6) : 1425 - 1436.

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