title: The phosphorylated form of connexin43 is up-regulated in breast hyperplasias and carcinomas and in their neoformed capillaries.
abstract: We applied an antiserum (SA226P) specifically recognizing the phosphorylated form of connexin43 (P-Cx43) to human breast samples including normal breast samples, with fibrocystic disease (FCD), fibroadenomas (FA), in situ and infiltrating carcinomas of all major types, and miscellaneous extramammary tumors. The findings were compared with those obtained with commercial antisera recognizing all Cx43 forms (pan-Cx43). A subset of samples was stained for Her2-neu and p44/42 to mitogen-activated protein kinase. Paraffin step sections were used. Immunoblots were performed on frozen samples of a representative subset of cases. In the normal breast, FCD, and FA, SA226P stained strongly and extensively most myoepithelial cells (MECs); luminal cells remained unstained. In proliferative FCD and some cellular FA, SA226P stained MEC and the capillary endothelium (CE). In ductal and lobular in situ carcinomas, SA226P reacted strongly and diffusely with the remaining MEC, the CE, and the transformed luminal cells. SA226P stained all infiltrating carcinomas except the tubular variant. In all breast carcinomas, the CE within and adjacent to tumors and some myofibroblasts stained with SA226P. By contrast, pan-Cx43 stained weakly and sporadically the MEC and rare samples of invasive carcinomas. Notably, Mab p44/42 reacted in parallel with the samples stained with SA226P, whereas reactions with Her2 were negative. Immunoblot findings paralleled those obtained immunohistochemically. We conclude that P-Cx43, restricted to MEC in the normal breast, is up-regulated in the same cells in hyperplasias and dysplasias and FA and is strongly up-regulated in invasive carcinomas. Notably, in some proliferative FCD and in most in situ and infiltrating carcinomas, P-Cx43 is strongly expressed in CE within and adjacent to the lesions but not away from them. These findings were paralleled by the strong nuclear reactions noted with Mab p44/42. These phenomena, although not exclusive to malignancy, are particularly conspicuous in breast carcinomas and seemingly reflect active proliferation associated with abnormal gap junctional intercellular communication.
authors.affiliation: Department of Patholgy, Rush Medical College, Chicago, IL 60611, USA.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Gould
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.forename: Kerstin
authors.initials: K
authors.lastname: Leykauf
authors.forename: Paolo
authors.initials: P
authors.lastname: Gattuso
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.forename: Angel
authors.initials: A
authors.lastname: Alonso
mesh_terms: D001940:Breast / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D001941:Breast Diseases / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D018031:Connexin 43 / Q000096:biosynthesis* / Q000737:chemistry; D004730:Endothelium, Vascular / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018226:Fibroadenoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D005348:Fibrocystic Breast Disease / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism* / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D018031:Connexin 43; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018719:Erb-b2 Receptor Tyrosine Kinases