Expression of connexins 26 and 43 in canine hyperplastic and neoplastic mammary glands
Expression of connexins 26 and 43 in canine hyperplastic and neoplastic mammary glands
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DOI：
10.1354/vp.42-5-633
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发表时间：
2005-09-01
影响因子：
2.4
通讯作者：
Dagli, MLZ
中科院分区：
文献类型：
--
作者：
Torres, LN;Matera, JM;Dagli, MLZ
间隙连接是在动物组织中发现的唯一的通信连接，由称为连接蛋白的蛋白质组成。连接蛋白表达的改变与肿瘤发生有关；在啮齿类动物和人类乳腺中，通常表达连接蛋白26和43的研究证实了这些变化在恶性肿瘤中的存在。乳腺肿瘤是犬类中第二常见的肿瘤，由于尚无关于犬类乳腺中连接蛋白的研究报道，因此本研究研究了连接蛋白26和43在正常、增生性和肿瘤性乳腺中的表达，以验证连接蛋白染色模式的改变是否与较高的细胞增殖和恶性表型有关。对4例正常乳腺、8例增生性乳腺、9例良性乳腺、51例恶性乳腺肿瘤进行连接蛋白26、连接蛋白43、E-cadherin、增殖细胞核抗原（PCNA）的免疫染色。正常乳腺、增生性乳腺和良性乳腺的连接蛋白26和43染色及细胞间e -钙粘蛋白染色呈点状。恶性肿瘤，尤其是侵袭性强且细胞增殖率高的肿瘤，要么表现为细胞膜间隙连接点较少，要么表现为细胞质免疫染色增加。恶性肿瘤E-cadherin的免疫染色也较弱；这种粘附分子的表达对于连接素到细胞膜的运输和形成通讯间隙连接是重要的。E-cadherin表达不足可能与连接蛋白的异常定位有关，并可能导致恶性表型。综上所述，狗恶性乳腺肿瘤中连接蛋白和E-cadherin的表达和分布与细胞增殖呈负相关，可能与其更具侵袭性的组织学类型和生物学行为有关。
Gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. Alterations in connexin expression have been associated with oncogenesis; reported studies in rodent and human mammary glands, which normally express connexins 26 and 43, confirm these alterations in malignancies. Mammary neoplasms represent the second most frequent neoplasm in dogs, and since there are no reports on the study of connexins in canine mammary glands, the present study investigated the expression of connexins 26 and 43 in normal, hyperplastic, and neoplastic mammary glands of this species, to verify if altered patterns of connexin staining are related to higher cell proliferation and malignant phenotypes. A total of 4 normal, 8 hyperplastic mammary glands, 9 benign, and 51 malignant mammary gland neoplasms were submitted for the immunostaining of connexins 26 and 43, E-cadherin, and proliferating cell nuclear antigen (PCNA). Normal, hyperplastic, and benign neoplastic mammary glands showed a punctate pattern for connexin 26 and 43 staining and an intercellular E-cadherin staining. Malignant neoplasms, especially the most aggressive cases with high cell proliferation rates, presented either fewer gap junction spots on the cell membranes or increased cytoplasmic immunostaining. Malignant tumors also expressed a less intense immunostaining of E-cadherin; the expression of this adhesion molecule is important for the transportation of connexins to cell membranes and in forming communicating gap junctions. Deficient expression of E-cadherin could be related to the aberrant connexin localization and may contribute to the malignant phenotype. In conclusion, the expression and distribution of connexins and E-cadherin are inversely correlated to cell proliferation in malignant mammary neoplasms of dogs and may well be related to their more aggressive histologic type and biologic behavior.