Connexin 32 expression reduces malignant phenotype in human A549 adenocarcinoma cells: Implication of Src involvement.
Recent evidence suggests that a member of the gap junction protein family, connexin (Cx) 32, acts as a tumor suppressor gene against lung adenocarcinoma. However, the precise mechanism remains unclear. In this study, we tried to explore the mechanism for the Cx32-dependent tumor-suppressive effect in lung adenocarcinoma. To perform this study, we established a stable clone of the human lung adenocarcinoma cell line, A549 in which the Cx32 gene was expressed. Cx32 expression in A549 cells reduced anchorage-independent growth and development of tumors in a xenograft model. Additionally, Cx32 induced contact inhibition of growth and reduced invasive activity in A549 cells. The tumor-suppressive effects of Cx32 depended on the inhibition of Src activity. These events were confirmed by an Src inhibitor (PP1) and siRNA for Cx32. These results suggest that the Cx32-dependent tumor-suppressive effect in A549 cells is explained by the inhibition of Src activity.
Hada
Sachio
S
Department of Food Science Research for Health, National Institute of Health and Nutrition, Toyama, Tokyo 162-8636, Japan.
Sato
Hiromi
H
Virgona
Nantiga
N
Hagiwara
Hiromi
H
Saito
Terunobu
T
Suzuki
Kazuyuki
K
Asano
Ryuji
R
Yano
Tomohiro
T
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014162:Transfection; D014183:Transplantation, Heterologous; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D019061:src-Family Kinases; D000097002:Gap Junction beta-1 Protein