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乳腺癌组织中Hedgehog相关蛋白的表达及其临床意义

刘志勇, 易 坚, 邹小明

刘志勇, 易 坚, 邹小明. 乳腺癌组织中Hedgehog相关蛋白的表达及其临床意义[J]. 肿瘤防治研究, 2014, 41(07): 756-761. DOI: 10.3971/j.issn.1000-8578.2014.07.015
引用本文: 刘志勇, 易 坚, 邹小明. 乳腺癌组织中Hedgehog相关蛋白的表达及其临床意义[J]. 肿瘤防治研究, 2014, 41(07): 756-761. DOI: 10.3971/j.issn.1000-8578.2014.07.015
LIU Zhiyong, YI Jian, ZOU Xiaoming. Expression of Hedgehog Related Proteins in Breast Carcinoma and Its Significance[J]. Cancer Research on Prevention and Treatment, 2014, 41(07): 756-761. DOI: 10.3971/j.issn.1000-8578.2014.07.015
Citation: LIU Zhiyong, YI Jian, ZOU Xiaoming. Expression of Hedgehog Related Proteins in Breast Carcinoma and Its Significance[J]. Cancer Research on Prevention and Treatment, 2014, 41(07): 756-761. DOI: 10.3971/j.issn.1000-8578.2014.07.015

乳腺癌组织中Hedgehog相关蛋白的表达及其临床意义

详细信息
    作者简介:

    刘志勇(1982-),男,硕士,主治医师,主要从事乳腺癌诊断、治疗及基因的研究

    通讯作者:

    易坚,E-mail:barton123321@163.com

  • 中图分类号: R737.9

Expression of Hedgehog Related Proteins in Breast Carcinoma and Its Significance

  • 摘要: 目的 探讨Hedgehog相关蛋白在乳腺癌中的表达及其临床意义。方法 从334例乳腺癌组织中制备组织块。免疫组织化学法检测六种Hedgehog信号蛋白(Shh、ptch、Smo、Gli-1、Gli-2和Gli-3)的表达。结果 Hedgehog信号蛋白表达与一些预后因素显著相关,包括淋巴结转移与Shh(P=0.001)、Gli-3 (P<0.001)、Ptch(P=0.025)的相关性、分期与Shh和Ptch表达(P分别为0.007和0.037)的相关性,核分级与Smo(P=0.004)和Gli-3(P=0.026)的相关性,组织学分级与Smo(P=0.007)的相关性。Shh、Ptch、Smo、Gli-1、Gli-2和Gli-3表达在表型之间差异有统计学意义(P分别为<0.0001、<0.0001、0.004、0.039、0.031和0.003)。Gli-2表达与较差的整体生存结果相关(P=0.012)。结论 Hedgehog通路表达激活与乳腺癌的侵袭性相关,可能是乳腺癌的一个有效的治疗靶点。Gli-2可作为乳腺癌的一个预后指标。

     

    Abstract: Objective To investigate the expression and clinical significance of Hedgehog related proteins in human primary breast carcinoma. Methods Tissue microarray blocks were prepared from 334 cases of breast carcinoma tissues. Immunohistochemical method was applied to analyze the expression of six Hedgehog signaling proteins, including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene Gli-1, Gli-2, and Gli-3. Results Expression of Hedgehog signaling proteins were significantly correlated with some prognostic factors, including the correlation of lymph node metastasis with the expression of Shh (P=0.001),Gli-3 (P<0.001) and Ptch(P=0.025), the correlation of staging with Shh and Ptch expression (P=0.007 and P=0.037, respectively), the correlation of nuclear grades with Smo and Gli-3 expression(P=0.004, P=0.026), and the correlation of histologic grades with Smo expression (P=0.007). The expression of Shh, Ptch, Smo, Gli-1, Gli-2 and Gli-3 were significantly different based on phenotypes (P=0.0001, P=0.0001, P=0.004, P=0.039, P=0.031 and P=0.003 respectively). Gli-2 expression was correlated with a worse overall survival (P=0.012). Conclusion The activation of Hedgehog pathway expression is correlated with the invasiveness of breast carcinoma. Hedgehog pathway may be a useful therapeutic target for breast carcinoma. Gli-2 could be a prognostic marker.

     

  • [1] Toftg?rd R. Hedgehog signalling in cancer[J].Cell Mol Life Sci,2000,57(12): 1720-31.
    [2] Gupta S,Takebe N,Lorusso P.Targeting the hedgehog pathway in cancer[J].Ther Adv Med Oncol,2010,2(4):237-50.
    [3] Katano M.Hedgehog signaling pathway as a therapeutic target in breast cancer[J].Cancer Lett,2005,227(2): 99-104.
    [4] Shahi MH,Rey JA,Castresana JS.The sonic hedgehog-GLI1 signaling pathway in brain tumor development[J].Expert Opin Ther Targets,2012,16(12):1227-38.
    [5] Rudin CM.Beyond the scalpel: targeting hedgehog in skin cancer prevention[J]. Cancer Prev Res (Phila),2010,3(1):1-3.
    [6] Bhatia B,Potts CR,Guldal C,et al.Hedgehog-mediated regulation of PPARγ controls metabolic patterns in neural precursors and shh-driven medulloblastoma[J].Acta Neuropathol,2012, 12 3(4):587-600.
    [7] Naqvi SH,Naqvi SH,Bandukda MY,et al.Present status and upcoming prospects of hedgehog pathway inhibitors in small cell lung cancer therapy[J]. Infect Agent Cancer,2013,8(1):17.
    [8] Huycke TR,Eames BF,Kimmel CB.Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone[J].Development,2012,139(13):2371-80.
    [9] Ristorcelli E,Lombardo D.Targeting Notch signaling in pancreatic cancer[J].Expert Opin Ther Targets,2010,14(5):541-52.
    [10] McKee CM,Xu D,Cao Y,et al.Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma[J].J Clin Invest,2012,122(11): 40 25-36.
    [11] Nakajima T,Iguchi T,Sato T.Hedgehog signaling plays roles in epithelial cell proliferation in neonatal mouse uterus and vagina[J].Cell Tissue Res,2012,348(1):239-47.
    [12] Das S,Samant RS,Shevde LA.The hedgehog pathway conditions the bone microenvironment for osteolytic metastasis of breast cancer[J].Int J Breast Cancer,2012,2012: 298623.
    [13] Onishi H,Katano M.Hedgehog signaling pathway as a therapeutic target in various types of cancer[J]. Cancer Sci,2011,102(10): 17 56-60.
    [14] Cooper MK,Wassif CA,Krakowiak PA,et al.A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis[J]. Nat Genet,2003,33(4):508-13.
    [15] Makinodan E,Marneros AG.Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and suppresses basal cell carcinoma of the skin[J].Exp Dermatol,2012,21(11):847-52.
    [16] Flora A,Klisch TJ,Schuster G,et al.Deletion of Atoh1 disrupts Sonic Hedgehog signaling in the developing cerebellum and prevents medulloblastoma[J]. Science, 2009, 326(5958): 1424-7.
    [17] Kubo M,Nakamura M,Tasaki A,et al.Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer[J]. Cancer Res,2004,64(17): 6071-4.
    [18] ten Haaf A,Bektas N,von Serenyi S,et al.Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival[J].BMC Cancer,2009,9:298.
    [19] O’Toole SA,Machalek DA,Shearer RF,et al.Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer[J].Cancer Res,2011,71(11): 4002-14.
    [20] Zhang D,Cao L,Li Y,et al.Expression of glioma-associated oncogene 2 (Gli 2) is correlated with poor prognosis in patients with hepatocellular carcinoma undergoing hepatectomy[J].World J Surg Oncol,2013,11: 25.
    [21] Ding YL,Wang QS,Zhao WM,et al.Expression of smoothened protein in colon cancer and its prognostic value for postoperative liver metastasis[J].Asian Pac J Cancer Prev,2012,13(8): 4001-5.
    [22] Lee SJ,Cho SH,Yoon JY,et al.Phase II study of S-1 monotherapy in paclitaxel- and cisplatin-refractory gastric cancer[J].Cancer Chemother Pharmacol,2009,65(1):159-66.
    [23] Lewis MT.Hedgehog signaling in mouse mammary gland development and neoplasia[J].J Mammary Gland Biol Neoplasia, 20 01,6(1):53-66.
    [24] Xuan Y,Lin Z.Expression of Indian Hedgehog signaling molecules in breast cancer[J].J Cancer Res Clin Oncol,2009,135(2): 235-40.
    [25] Goldhirsch A,Wood WC,Coates AS,et al.Strategies for subtypes- -dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011[J].Ann Oncol,2011,22(8):1736-47.
    [26] Nagaria TS,Williams JL,Leduc C,et al.Flavopiridol synergizes with sorafenib to induce cytotoxicity and potentiate antitumorigenic activity in EGFR/HER-2 and mutant RAS/RAF breast cancer model systems[J]. Neoplasia,2013,15(8):939-51.
    [27] Green JL,La J,Yum KW,et al.Paracrine Wnt signaling both promotes and inhibits human breast tumor growth[J].Proc Natl Acad Sci U S A,2013,110(17):6991-6.
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出版历程
  • 刊出日期:  2014-07-24

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