title: Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.
abstract: Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.
authors: a Department of General Pathomorphology , Medical University of Bialystok , Bialystok , Poland .
authors: Urszula
authors: U
authors: Sulkowska
authors: b Department of Anatomy, Faculty of Health Sciences , Jan Kochanowski University , Kielce , Poland , and.
authors: Andrzej
authors: A
authors: Wincewicz
authors: c Department of Pathology , Maria Curie-Sklodowska Bialystok Oncology Center , Bialystok , Poland.
authors: Luiza
authors: L
authors: Kanczuga-Koda
authors: a Department of General Pathomorphology , Medical University of Bialystok , Bialystok , Poland .
authors: Mariusz
authors: M
authors: Koda
authors: a Department of General Pathomorphology , Medical University of Bialystok , Bialystok , Poland .
authors: Stanislaw
authors: S
authors: Sulkowski
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology; D000072259:Connexin 26; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010766:Phosphorylation; D011980:Receptors, Progesterone / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494772:BAK1 protein, human; D018031:Connexin 43; D017630:Connexins; D047628:Estrogen Receptor alpha; C000607042:GJB2 protein, human; D011980:Receptors, Progesterone; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; D000072259:Connexin 26
keywords: Apoptosis; connexins; endometrioid adenocarcinoma; estrogen and progesterone receptors