乳腺癌浸润转移的研究进展

来源：岁月联盟 作者：王丽梅，杨拯，张晓 时间：2015-05-10

    2.3  内皮素

    内皮素(Endothelin1,ET1)是一种血管活性肽。近年来研究表明ET1的生物活性不仅限于心血管系统，它对全身组织都具有重要的生物学作用。ET1对细胞DNA的合成，原始基因的表达以及增殖均有影响。已证明肺癌、胰腺癌、结肠癌、子宫颈癌和乳腺癌中存在ET1。在乳腺癌研究中发现ET1标记阳性率及其在阳性细胞中的含量以Ⅲ级乳腺癌最高、Ⅱ级次之、Ⅰ级最低。因此，ET1的过量表达可能导致细胞恶性生长或恶性度增高[31-32]。

    2.4组织蛋白酶Ｂ

    组织蛋白酶Ｂ(Cathepsin)是一种半胱氨酸蛋白，在肿瘤细胞的蛋白质代谢中起重要作用，而且直接或间接的影响瘤细胞外基质的溶解。此酶在非小细胞肺癌中的表达很高，而且阳性者比阴性者术后生存期短，还发现有淋巴转移者阳性率明显高于未转移者。结肠癌、胰腺癌、胃癌和乳腺癌中的研究中也发现组织蛋白酶Ｂ的表达与这些肿瘤的浸润转移有关[33]。

    2.5  组织蛋白酶Ｄ

    组织蛋白酶Ｄ（CathD）分子量为34KD蛋白质。它低浓度存在于各种细胞中,在正常或小叶增生的乳腺组织中,浓度都很低,可以忽略不计。CathD能刺激细胞生长，并能溶解基底膜，细胞外基质和结缔组织。CathD能刺激MCF7的细胞增生，MCF7细胞能释放125I标记的碱性成纤维细胞生长因子(125IbFGF)进入细胞外基质，具有促有丝分裂作用。这在血管生成中可能起着非常重要的作用，是肿瘤转移的重要步骤。研究表明乳腺癌细胞中CathD高表达促进癌细胞浸润和扩散。原发乳腺癌提取物中高浓度的CathD和随后发生的转移危险性高度相关。这是由于在酸性PH中自体激活后，对基底膜和糖蛋白等不同底物进行蛋白水解；另外，它促进MCF7细胞的有丝分裂，说明CathD与表达程度与乳癌浸润扩散密切相关。在腋淋巴结阴性(ANN)的乳腺癌人中，高CathD者复发的相对危险性是较低者的7-10倍[34-35]。

    综上所述，可见癌基因，抑癌基因和细胞粘附分子、胞浆蛋白和酶类在肿瘤的发生和转移过程中具有重要作用，所以，进一步研究它们的分子机制及作用，对肿瘤及其转移的治疗、预后具有重要的临床价值。

【参考文献】
  1 Saegusa M, Hashimura M, Hara A, et al; Loss of expression of the gene deleted in colon carcinoma (DCC) is closely related to histologic differentiation and lymph node metastasis in endometrial carcinoma[J]. Cancer, 1999, 85(2): 453-464.

2 Saegusa M, Machida D, Okayasu I. Loss of DCC gene expression during ovarian tumorigenesis: relation to tumor differetiation and progression[J]. British J of Cancer, 2000, 82: 571-578.

3 Lassus H, Salovaara R, Aaltonen LA, et al.Allelic analysis of serous ovarian carcinoma reveals two putative tumor suppressor loci at 19q22q23distal to SMAD4, SMAD2, and DCC[J]. Am J Pathology, 2001, 159: 35-42.

4 Schwarte Waldhoff I, Klein S, Blass Kampmann S, et al.DPC4/SMAD4 mediated tumor suppression of colon carcinoma cells is associated with reduced urokinase expression[J]. Oncogene, 1999, 18: 203152-203158.

5 Koyama M, Ito M, Nagai H, et al. Inactivation of both alleles of the DPC4/SMAD4 gene in advanced colorectal cancers: identification of seven novel somatic mutations in tumors from Japanese patients[J]. Mutat Res, 1999, 406: 2-4, 71-77.

6 Kawabata M, Imamura Y, Inoue H, et al. Intracellular signaling of the TGFB, superfamily by smad proteins[J]. Ann N Y Acad Sci, 1999, 886: 73-82.

7 Hunt KK, Fleming JB, Abramian A, et al. Over expression of the tumor suppressor gene Smad4/DPC4 induces p21waf1 expression and growth inhibition in human carcinoma cells[J]. Cancer Res, 1998, 58: 245656-245661.

8 Espinosa de los Monteros A, Mill n MY, Ram rez GA, et al. Expression of maspin in mammary gland tumors of the dog[J]. VetPathol, 2005, 42(3): 250-257.

9 Shi HY. Modeling human breast cancer metastasis in mice: maspin as a paradigm[J]. HistolHistopathol, 2003, 8(1): 201-206.

10 Sato N, Fukushima N, Mat subayashi H, et al. Identification of maspin and S100P as novel hypomet hylation target sin pancreatic cancer using global gene expression profiling[J]. Oncogene, 2004, 23(8):1531-1538.

11 Bieche I, Girault I, Sabourin JC, et al. Prognostic value of maspin mRNA expression in ER alphapositive postmenopausal breast carcinomas[J]. Br J Cancer, 2003, 88 (6): 863-870.

12 Dai JL, Wang L, Sahin AA, et al. NHERF (Na+/H+ exchanger regulatory factor) gene mutations in human breast cancer[J]. Oncogene, 2004, 23(53): 8681-8687.

13 DeFazio A, Chiew YE, Sini RL,et.al. Expression of cerbB receptors,heregulin and oestrogen receptor in human breast cell lines[J]. IntJCancer, 2000, 87(4): 487-498.

14 Offterdinger M, Schneider SM, Huber H, et.al. Expression of cerbB4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3[J]. BiochemBiophysResCommun. 1999, 258(3): 559-564.

15 Gago FE, Fanelli MA, Ciocca DR. Coexpression of steroid hormone receptors (estrogen receptor and/or progesterone receptors)and Her2/neu(cerbB2)in breast cancer: Clinical outcome following tamoxifen based adjuvant therapy[J]. J Steroid Biochem Mol Biol, 2006, 98(1): 36-40.

16 Rom J, Aulmann S, Schneeweiss A, et al. Comparison of immunehistological parameters in primary breast cancers and corresponding locoregional recurrences[J]. Pathol Res Pract, 2006, 202(3): 125-130.

17 Ring S, Ellis P A. Predictors of response to systemic therapy in breast cancer[J]. Forum(Genova), 2002, 12(1): 19-32.

18 Tsut sui S, Ohno S, Murakami S, et al. Prognostic value of CerbB2 expression in breast cancer[J]. J Surg Oncol, 2002, 79(4): 216-231.

19 Rudland PS, PlattHiggins A, ElTanani M, et al. Prognostic significance of the metastasisassociated protein osteopontin in human breast cancer[J]. CancerRes. 2002, 62(12): 3417-3427.

20 Xu L, Tang WH. Systemic p53 gene therapy of cancer with immunelipoplexes targeted by antitransferrin receptor scFv[J]. MolMed, 2001, 7(10): 723-734.

21 Costa C, Soares R, ReisFilho JS,et.al. Cyclooxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer[J]. JClinPathol. 2002, 55(6): 429-434.

22 Seeger H, Wallwiener D, Kraemer E, et.al. Comparison of possible carcinogenic estradiol metabolites: effects on proliferation, apoptosis and metastasis of human breast cancer cells[J]. Maturitas, 2006, 54(1): 72-77.

23 Gupta A, Inaba S, Wong OK, et al. Breast cancer2 specific gene1 interact s wit h t he mitotic checkpoint kinase BubR1[J]. Oncoene, 2003, 22(48): 7593-7599.

24 Gupta A, Godwin AK, Vanderveer L, et al. Hypomet hylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma[J]. Cancer Res, 2003, 63(3): 664-673.

25 Lu A, Gupta A, Li C, et al. Molecular mechanisms for aberrant expression of the human breast cancer specic gene1 in breast cancer cells: control of transcription by DNA met hylation and intronic sequences[J]. Oncogene, 2001, 20(37): 5173-5185.

26 Lu A, Zhang F, Gupta A, et al. Blockade of AP1 Transactivation Abrogates t he Abnormal Expression of Breast Cancer specific Gene1 in Breast Cancer Cells[J]. J Biol Chem, 2002, 277(35): 31364-31372.

27 Bruening W, Giasson B I, Klein2Szanto A J, et al. Synucleins areexpressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary[J]. Cancer, 2000, 88(9): 21542163.

28 Abdul Rasool S, Kidson S H, Panieri E, et al. An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes Journal Of Clinical Pat hology[J]. J Clin Pathol, 2006, 59(3): 289-297.

29 Zhu L, Lam C K, Chow L W. Sentinel Lymph Node biopsy or detection of micrometastasis in bone marrow: which might be an alternative lymph node dissection in breast cancer patient s[J]. Asian J Surg, 2004, 27(4): 279-283.

30 Parker C, Rampaul RS. Ecadherin as a prognostic indicator in primary breast cancer[J]. BrJCancer. 2001, 85(12):1958-1963.

31 W lfing P, G tte M, Sonntag B, et.al. Overexpression of EndothelinAreceptor in breast cancer: regulation by estradiol and cobaltchloride induced hypoxia[J]. IntJOncol, 2005, 26(4): 951-960.

32 W lfing P, Diallo R, Kersting C, et.al. Expression of endothelin1,endothelinA,and endothelinB receptor in human breast cancer and correlation with longterm followup[J]. ClinCancerRes. 2003, 9(11): 4125-4131.

33 Glondu M, LiaudetCoopman E, Derocq D, et al. Downregulation of cathepsinD expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells[J].Oncogene. 2002, 21(33): 5127-5134.

34 Wolf M, ClarkLewis I, Buri C, et al. Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein1 alpha, macrophage inflammatory protein1 beta, and SLC that are expressed in human breast cancer[J]. AmJPathol, 2003, 162(4):11831190.

35 Isola J, Weitz S, Visakorpi T, et al. Cathepsin D expresion detected by immunehistochemity has independent prognostic value in axillary nodenegative breast cancer[J]. J. clin Oncol.1993, 11: 863-877.

上一篇：雷公藤的毒性研究及对策
下一篇：糖尿病血管病变的药物治疗进展

图片内容

最近更新

随机推荐