Suppressed gap junctional intercellular communication in carcinogenesis of endometrium.
To examine whether and at which stage of endometrial carcinogenesis decreased connexin expression occurs, we investigated changes in the expression of the gap junction proteins, connexin 26 (Cx26), Cx32 and Cx43, in human endometrial hyperplasia and cancer samples. Forty-eight endometrial tissue samples (15 endometrial hyperplasias and 33 endometrial cancers) were subjected to immunofluorescence and RT-PCR analysis. In endometrial hyperplasia, Cx26 was aberrantly expressed in all samples as revealed immunohistochemically. There was weak or negative expression in 12 samples (80.0%) and diffuse expression in cytoplasm in 3 samples (20.0%). Cx32 expression in those samples was similar to that of Cx26; there was weak or negative expression in 11 samples (73.3%) and diffuse expression in 4 samples (26.7%). In endometrial cancer, Cx26 was expressed weakly or negatively in 25 samples (75.8%), diffusely in 6 samples (18.2%) and normally in 2 samples (6.1%), while Cx32 was expressed weakly or negatively in 26 samples (78.8%), diffusely in 5 samples (15.2%) and normally in 2 samples (6.1%). It was confirmed that weak staining of Cx26 and Cx32 was due to poor expression of their mRNA. All samples showed weak Cx43 protein expression as revealed by immunohistochemical analysis. In the majority of samples, concomitant expression levels of Cx26 and Cx32 protein were observed, confirming our long-term hypothesis that Cx26 and Cx32 are both abnormally regulated in a coordinated fashion in the endometrium. Our results indicate that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur due to the suppressed expression and the aberrant localization of connexin at relatively early stages.
Saito
T
T
Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan. tsaito@sapmed.ac.jp
Nishimura
M
M
Kudo
R
R
Yamasaki
H
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002450:Cell Communication; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
D000072259:Connexin 26; D018031:Connexin 43; D017630:Connexins; D017931:DNA Primers; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein; C000607042:GJB2 protein, human