Connexin32 inhibits gastric carcinogenesis through cell cycle arrest and altered expression of p21Cip1 and p27Kip1.
Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and p21(Cip1) and p27(Kip1) expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting. Immunohistochemical study noted a strong inverse correlation between Cx32 and Ki67 expression pattern as well as their location. In vitro, overexpression of Cx32 in AGS cells inhibited cell proliferation significantly. G1 arrest, up-regulation of cell cycle-regulatory proteins p21(Cip1) and p27(Kip1) was also found at both mRNA and protein levels. Taken together, Cx32 plays some roles in gastric cancer development by inhibiting gastric cancer cell proliferation through cell cycle arrest and cell cycle regulatory proteins.
Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Korea.
Hyang
H
Jee
Su-Hyung
SH
Lee
Jun-Won
JW
Park
Bo-Ram
BR
Lee
Ki-Taek
KT
Nam
Dae-Yong
DY
Kim
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019394:Ki-67 Antigen; D000097002:Gap Junction beta-1 Protein