The expression of gap junctional proteins during different stages of mouse skin carcinogenesis.
The loss or alteration of gap junctional intercellular communication (GJIC) has long been proposed to play an important role in the process of carcinogenesis. In this study we examined the expression of three gap junction proteins, connexins (Cx)26, 43 and 31.1, in mouse hyperplastic skin, papillomas and squamous cell carcinomas (SCC). Tumors were induced in SENCAR mice by either of two initiation/promotion protocols: 7,12-dimethylbenz-[a] anthracene (DMBA)/12-O-tetradecanoyl-phorbol-13-acetate (TPA) or DMBA/benzoyl-peroxide (BzPo). Keratinocytes in adult mouse skin expressed Cx31.1 and Cx43 but did not express Cx26. Skin hyperplasia induced by one topical application of TPA was accompanied by hyperexpression of both Cx26 and Cx43. In addition, TPA significantly inhibited the expression of Cx31.1. After repetitive application. Connexin 26 and Cx43 were hyperexpressed in most of the papillomas studied (20-40 weeks after initiation). However, in some late papillomas, immunostaining revealed a focal loss of Cx26. Immunostaining of mouse skin SCC revealed decreased Cx43 and Cx26 levels in 65% and 85% of cases respectively. The high levels of Cx26 and Cx43 mRNA in most of the SCC did not correlate with the decreased abundance or disappearance of Cx26 and Cx43 immunoreactive spots from tumor plasma membranes. Thus, the expression of these two connexins in SCC was impaired at the post-translation level. Cx31.1 expression was strongly inhibited during all stages of carcinogenesis. Taken together, our results suggest that three different connexin genes are differentially regulated during mouse skin carcinogenesis and the decrease of connexin expression may be an important marker of skin tumor expression.
Budunova
I V
IV
University of Texas M.D. Anderson Cancer Center, Science Park Research Division, Smithville 78957, USA.
Carbajal
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S
Slaga
T J
TJ
D000818:Animals; D002450:Cell Communication; D000072259:Connexin 26; D018031:Connexin 43 / Q000032:analysis* / Q000235:genetics; D017630:Connexins / Q000032:analysis* / Q000235:genetics; D005260:Female; D006965:Hyperplasia; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000648:ultrastructure
D018031:Connexin 43; D017630:Connexins; C000607043:Gjb2 protein, mouse; D012333:RNA, Messenger; C076274:connexin 31.1; D000072259:Connexin 26