Jamieson S, Going J J, D'Arcy R, George W D
Department of Surgery, Western Infirmary, Glasgow, U.K.
J Pathol. 1998 Jan;184(1):37-43. doi: 10.1002/(SICI)1096-9896(199801)184:1<37::AID-PATH966>3.0.CO;2-D.
Gap junctional intercellular communication (GJIC) has been proposed as a cellular mechanism for tumour suppression and there is experimental evidence in support of this. If aberrant GJIC contributes to the formation of human breast tumours, one might expect that the connexins (gap junction proteins) expressed by epithelial cells in normal human breast would be down-regulated in tumour epithelial cells, or that tumour cells might show aberrant expression of other connexin family members. This study examines the immunocytochemical expression of connexins 26 (Cx26) and 43 (Cx43) in normal human breast, 11 benign breast lesions, two special-type carcinomas, and 27 invasive carcinomas of no special histological type (NST). Cx26 generally was not expressed at detectable level in normal human breast, but punctate Cx43 immunostaining of the myoepithelial cells was found. Cx43 staining of the myoepithelium was also a feature of the benign lesions and ductal carcinoma in situ (DCIS). In general, the epithelial cells of benign lesions failed to stain for either connexin. Similarly, a lobular carcinoma did not express Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of a mucoid carcinoma. Cx26 was up-regulated in the carcinoma cells of 15 of the 27 invasive NST carcinomas, although the staining was usually cytoplasmic and heterogeneous. Cx43 was expressed by stromal cells, possibly myofibroblasts, in all NST carcinomas. Furthermore, there was heterogeneous Cx43 expression in the carcinoma cells of 14 of the 27 NST carcinomas and the staining was often intercellular and punctate, characteristic of functional connexins. Up-regulated of Cx26 and/or Cx43 in the carcinoma cells of over two-thirds of invasive lesions of NST is not necessarily inconsistent with a tumour suppressor role for GJIC. However, the role of gap junctions in the formation and progression of solid human tumours is likely to be more complex than indicated from experimental systems.
间隙连接细胞间通讯（GJIC）已被提出作为一种肿瘤抑制的细胞机制，并且有实验证据支持这一点。如果异常的GJIC促成人类乳腺肿瘤的形成，那么人们可能会预期，正常人类乳腺上皮细胞表达的连接蛋白（间隙连接蛋白）在肿瘤上皮细胞中会下调，或者肿瘤细胞可能会显示出其他连接蛋白家族成员的异常表达。本研究检测了连接蛋白26（Cx26）和43（Cx43）在正常人类乳腺、11例良性乳腺病变、2例特殊类型癌以及27例无特殊组织学类型（NST）的浸润性癌中的免疫细胞化学表达。Cx26在正常人类乳腺中一般未在可检测水平表达，但发现肌上皮细胞有散在的Cx43免疫染色。肌上皮细胞的Cx43染色也是良性病变和导管原位癌（DCIS）的一个特征。一般来说，良性病变的上皮细胞两种连接蛋白均未染色。同样，小叶癌不表达Cx26或Cx43，但黏液癌的上皮细胞中有散在的Cx43。在27例浸润性NST癌中的15例癌细胞中，Cx26上调，尽管染色通常为细胞质且不均匀。在所有NST癌中，Cx43由基质细胞表达，可能是肌成纤维细胞。此外，27例NST癌中的14例癌细胞中Cx43表达不均匀，染色通常为细胞间且散在，是功能性连接蛋白的特征。在超过三分之二的NST浸润性病变的癌细胞中Cx26和/或Cx43上调不一定与GJIC的肿瘤抑制作用相矛盾。然而，间隙连接在人类实体肿瘤形成和进展中的作用可能比实验系统所显示的更为复杂。
