PMID- 10506104 OWN - NLM STAT- MEDLINE DCOM- 19991104 LR - 20231213 IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 20 IP - 10 DP - 1999 Oct TI - Gap junction proteins connexin32 and connexin43 partially acquire growth-suppressive function in HeLa cells by deletion of their C-terminal tails. PG - 1913-8 AB - Our laboratory has previously reported that transfection of a connexin26 (Cx26) gene, but not connexin40 nor connexin43 (Cx43), into HeLa cells expressing no detectable level of connexins suppressed the tumorigenic phenotype of the HeLa cells both in vitro and in vivo, although all of these connexins induced gap junctional intercellular communication in HeLa cells to a similar extent. The most remarkable structural difference between connexin proteins is the length of the C-terminal cytoplasmic tail, Cx26 having almost no tail, while Cx43 and connexin32 (Cx32) have long and intermediate ones, respectively. When Cx32 and Cx43 lose their C-terminal tails, they seem to resemble Cx26 in structure. To examine whether such truncated connexins become tumor suppressive in HeLa cells, we introduced a stop codon into each of the Cx32 and Cx43 cDNAs to remove their C-terminal tails and transfected these constructs (DeltaCx) into HeLa cells. Both DeltaCx cDNAs induced GJIC as efficiently as the wild-type counterparts. Although none of the truncated connexins affected proliferation rate, the truncated Cx32 and Cx43 proteins suppressed anchorage-independent cell growth in soft agar. Furthermore, when the transfectants were injected into the backs of nude mice, tumor appearance was delayed by 7 days in animals given cells expressing truncated connexins, i.e. tumors became detectable on days 11 and 18 after injection of vector and DeltaCx transfectants, respectively. Although throughout these experiments the truncated connexins did not completely eliminate the tumorigenicity of HeLa cells, as Cx26 did, it was evident that deletion of the C-terminal tails gave both Cx32 and Cx43 a capacity for negative growth control, suggesting that the C-terminal tails of these two connexins function as a regulatory region for connexin-mediated growth control in HeLa cells. FAU - Omori, Y AU - Omori Y AD - Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France. FAU - Yamasaki, H AU - Yamasaki H LA - eng GR - R01-CA-40534/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (GJB2 protein, human) RN - 127120-53-0 (Connexin 26) SB - IM MH - Animals MH - Cell Communication/genetics MH - Cell Division/*physiology MH - Connexin 26 MH - Connexin 43/genetics/*physiology MH - Connexins/genetics/*physiology MH - HeLa Cells MH - Humans MH - Immunohistochemistry MH - Mice MH - Mice, Nude MH - Phenotype MH - Sequence Deletion MH - Transfection MH - Gap Junction beta-1 Protein EDAT- 1999/10/03 00:00 MHDA- 1999/10/03 00:01 CRDT- 1999/10/03 00:00 PHST- 1999/10/03 00:00 [pubmed] PHST- 1999/10/03 00:01 [medline] PHST- 1999/10/03 00:00 [entrez] AID - 10.1093/carcin/20.10.1913 [doi] PST - ppublish SO - Carcinogenesis. 1999 Oct;20(10):1913-8. doi: 10.1093/carcin/20.10.1913.