title: Altered expression of connexins in urethane-induced mouse lung adenomas.
abstract: Lung carcinogenesis is a multistep process whose molecular alterations can be studied in mouse models. Urethane, a specific lung tumor carcinogen, can induce adenomas in mice. Mouse lung alveolar cells reportedly generate lung neoplasms, and express connexins 26, 32, 43 and 46. The aim of the present study was to evaluate the expression of connexins in urethane-induced lung adenomas. Fifteen-day-old CD1 male mice received 2 i.p. injections of urethane (1.5 g/kg bw). The mice were euthanized 25 weeks after urethane injection, and lung adenomas were quantified. Lung tissue and lung adenomas were harvested and the RNA was extracted. The expression of connexins 26, 32, 43 and 46 was evaluated by Real-Time PCR, and these proteins were identified by Western blot. Immunohistochemistry revealed the distribution pattern of these connexins in lung tissue and adenomas. The treatment with urethane was associated with the downregulation of Cx26, 32 and 46 expressions, and with the upregulation of Cx43 expression in lung tissue. Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present. Western blot and immunohistochemistry corroborated the RT-PCR data. These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors. The role of Cx26 and Cx46 is yet to be determined.
authors.affiliation: Laboratory of Experimental Oncology, Department of Pathology, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, Brazil.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Avanzo
authors.forename: Marc
authors.initials: M
authors.lastname: Mesnil
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Hernandez-Blazquez
authors.forename: Tereza Cristina
authors.initials: TC
authors.lastname: da Silva
authors.forename: Heidge
authors.initials: H
authors.lastname: Fukumasu
authors.forename: Claudia Madalena Cabrera
authors.initials: CM
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Maria Lúcia Zaidan
authors.initials: ML
authors.lastname: Dagli
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014520:Urethane / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D017630:Connexins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014520:Urethane