Negative growth control of renal cell carcinoma cell by connexin 32: possible involvement of Her-2.
Connexin (Cx) genes have negative growth effects on tumor cells with certain cell specificity. We have previously reported that Cx32 is specifically downregulated in human renal cell carcinoma cell (RCC) lines as well as cancerous regions of kidneys and that the Cx is expressed in the progenitor cells of the carcinoma. However, the precise role of Cx32 in growth control of RCC cells remains unknown. In this study, we examined whether Cx32 could act in growth control against a human RCC cell, Caki-2 cell. In order to estimate the cell growth control, we established Caki-2 cells that have stable expression of Cx32 genes. Cx32 expression in Caki-2 cells induced contact inhibition of growth and reduced anchorage-independent growth ability, but did not significantly affect lag phase growth rates. This growth control by Cx32 was dependent on the inhibition of the cell-cycle transition from G1 to S phase at high cell density, and the inhibition of the cell-cycle transition related to the suppression of Her-2 activation. Furthermore, the suppression of Cx32 expression in Caki-2 cells by short interfering RNA induced the activation of Her-2. These data suggest that Cx32 has negative growth control of Caki-2 cells, partly due to the inhibition of the Her-2 activation.
Fujimoto
Eriko
E
Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
Satoh
Haruna
H
Negishi
Etsuko
E
Ueno
Koichi
K
Nagashima
Yoji
Y
Hagiwara
Kiyokazu
K
Yamasaki
Hiroshi
H
Yano
Tomohiro
T
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division; D017630:Connexins / Q000502:physiology*; D003260:Contact Inhibition; D016193:G1 Phase; D017629:Gap Junctions / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016196:S Phase; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000097002:Gap Junction beta-1 Protein