NEGATIVE GROWTH-CONTROL OF HELA-CELLS BY CONNEXIN GENES - CONNEXIN SPECIES-SPECIFICITY

In order to examine whether different connexin gene species exert diff erent degrees of tumor-suppressing activity, we characterized growth c haracteristics of a gap junction-deficient human cancer cell line, HeL a cells, before and after transfection with cDNA for three different c onnexins, connexin (ex) 26, ex 40, and ex 43. Ah transfected cell line s (3 clones transfected with the ex 26 gene, 2 clones with ex 40, and 1 with ex 43) showed establishment of gap junctional intercellular com munication (GJIC). Two of the ex 26-transfected clones showed signific antly slower growth compared with the parental HeLa cells. When transf ectants were grown in soft agar, the three ex 26-transfected clones gr ew much less than the other transfectants and parent HeLa cells. When injected into nude mice, the two ex 26 clones which exhibited the high est amount of ex 26 transcript induced almost no tumors, whereas other transfectants, including the cs 26 clone which exhibited the lowest a mount of ex 26 transcript, were tumorigenic. Among transfectants of va rious connexin genes, there was no good inverse correlation between th eir GJIC and tumorigenicity. GJIC levels were significantly higher in tumors induced in nude mice by clone ex 26 A and E transfectants. Thes e results suggest that all of the connexin genes examined could induce recovery of GJIC of HeLa cells, but only the ex 26 gene exerts strong negative growth control on HeLa cells; thus, this connexin gene may h ave different functions from other connexin genes.