The gap junction protein connexin32 is a mouse lung tumor suppressor.
Although loss of connexin expression and/or gap junction intercellular communication correlates with decreased growth control and increased neoplastic potential, there is limited evidence directly linking gap junction intercellular communication function with tumor suppression in situ. Here, we show for the first time that a gap junction protein, connexin32 (Cx32), acts as a lung tumor suppressor in a mouse model. Cx32-deficient nontumorous lung tissue exhibited an increased proliferative index (P < 0.001), and, after exposure to the carcinogen diethylnitrosamine, Cx32-deficient mice exhibited a highly statistically significant (P < 0.001) increase in bronchioloalveolar lung tumor incidence (28 of 45, 62%) and a 45% increase in average multiplicity compared with wild-type mice (7 of 29, 24%). Tumors from Cx32-deficient mice also showed increased activation of mitogen-activated protein kinase (P < 0.001) compared with wild-type tumors, implicating this signaling pathway in Cx32/gap junction intercellular communication-associated lung tumorigenesis.
King
Timothy J
TJ
Cancer Prevention Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, and Department of Pathobiology, University of Washington, Seattle, Washington, USA. tking@fhcrc.org
Lampe
Paul D
PD
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D017630:Connexins / Q000172:deficiency* / Q000502:physiology; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C; D000097002:Gap Junction beta-1 Protein
D001973:Bromodeoxyuridine; D017630:Connexins; D004052:Diethylnitrosamine; D036341:Intercellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D000097002:Gap Junction beta-1 Protein; C489680:Sftpc protein, mouse