title: Thyroid cell proliferation in response to forced expression of gap junction proteins.
abstract: Gap junctions are known to play a role in the control of cell proliferation, and connexins (Cx) are considered to be tumor suppressors. However, the effects of Cx on cell proliferation are dependent on the Cx which is expressed and on the cell type under consideration. We previously found that restoration of cell-to-cell communication by stable transfection of two independent thyroid-derived cell lines, FRTL-5 and FRT cells, with the Cx32 gene induced a marked reduction of their proliferation rate. This study aimed i) at determining whether Cx43, which is coexpressed with Cx32 by thyroid epithelial cells, exerts the same action as Cx32 on cell proliferation and ii) at identifying alterations of the cell cycle control system that might account for the Cx32-induced proliferation slowdown in thyrocytes. In contrast with previous data on different epithelial cell types, we report that restoration of intercellular communication in FRTL-5 and FRT cells by stable expression of Cx43 did not modify their proliferation properties. Cell cycle analyses revealed that the Cx32-induced proliferation slow-down was related to a lengthening of the G1 phase. The level of expression of two regulatory proteins of the Cip/Kip cyclin-dependent kinase inhibitor family, p27kip1 and p2cip1, was increased in the two cell lines expressing Cx32. In conclusion, Cx32 and Cx43, physiologically coexpressed by thyrocytes, have a differential impact on thyroid cell proliferation in vitro. The cyclin-dependent kinase inhibitors, p27kip1 and p21cip1 might represent cell cycle effectors relaying the down-regulatory effect of Cx32 on the proliferation of thyroid epithelial cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Lyon-RTH Laennec, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Flachon
authors.forename: Hélène
authors.initials: H
authors.lastname: Tonoli
authors.forename: Samia
authors.initials: S
authors.lastname: Selmi-Ruby
authors.forename: Christine
authors.initials: C
authors.lastname: Durand
authors.forename: Rachida
authors.initials: R
authors.lastname: Rabilloud
authors.forename: Bernard
authors.initials: B
authors.lastname: Rousset
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Munari-Silem
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D017630:Connexins; D005456:Fluorescent Dyes; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human