- Cancer du Testicule
- Published:
Localisation aberrante de la connexine 43 dans le cancer du testicule
Aberrant localization of connexin 43 in testicular cancer
Andrologie volume 11, pages 56–62 (2001)
Résumé
La communication intercellulaire via les jonctions gap (GJIC, pour «Gap Jonction Intercellular Communication») est un mode ubiquitaire de dialogue entre les cellules. Il participe au contrôle de la prolifération cellulaire. Des troubles de l’expression des connexines (Cx), les protéines transmembranaires constitutives de ces canaux intercellulaires, ont souvent été associés au phénotype malin. Dans le tube séminifère, la Cx43 est exprimée majoritairement par les cellules de Sertoli et les cellules germinales basales. L’expression de la Cx43 a été étudiée dans une série de 4 cancers du testicule comprenant une prolifération séminomateuse exclusive, à un stade T1-2 N0 M0. Les transcrits et la protéine analysés par RT-PCR et Western blot, ont été retrouvés dans tous les cas, à la taille attendue. La protéine étudiée par immunofluorescence indirecte était délocalisée au sein du cytoplasme, non exprimée à la membrane, excluant sa participation à une éventuelle GJIC. La signification de cette localisation aberrante de la Cx43 est discutée dans le cadre des relations GJIC/tumorigenèse.
Abstract
Most cells can communicate directly via gap junction channels. Gap junction intercellular communication (GJIC) participates in the control of cell proliferation. Abnormal expression of connexins (Cx), the constitutive proteins of gap junctions, has been associated with a transformed phenotype. In the seminiferous tubules, connexin Cx43 is predominantly expressed by Sertoli cell and germinal cell membranes. We studied Cx43 expression in four testicular cancers (pure seminoma). Cx43 mRNA and protein characterized by RT PCR and Western blot were found to be similar to controls (normal testes) in each case. However, immunofluorscence study of Cx43 protein indicated a cytoplasmic localization with no membrane expression, excluding the participation of Cx43 in GJIC. The significance of this aberrant localization will be discussed in relation to carcinogenesis.
Références
BATIAS C., DEFAMIE N., LABLACK A.,et al.: Modified expression of testicular gap junction connexin 43 during normal spermatogenic cycle and in altered spermatogenesis. Cell. Tissue Res., 1999, 298:113–121.
BATIAS C., SIFFROI J.P., FÉNICHEL P., POINTIS G., SEGRETAIN D.: Connexin43 gene expression and regulation in the roddent seminiferous epithelium. J. Histochem. Cytochem., 2000, 48:793–805.
BERTHOUD V.M., LEDBETTER M.L., HERTZBERG E.L., SAEZ J.C.: Connexin 43 in MDCK cells: regulation by a tumor-promoting phorbol ester and Ca2+. Eur. J. Cell. Biol., 1992, 57: 40–50.
BRUZZONE R., WHITE TW., PAUL D.: Connexions with connexins: the molecular basis of direct intercellular signaling. Eur. J. Biochem., 1996, 238:1–27.
COCHAND-PRIOLLET B., RAISON D., MOLINIE V., GUILLAUSSEAU P.J., WASSEF M., BOUCHAUD C.: Altered gap and tight junctions in human thyroid oncocytic tumors: a study of 8 cases by freeze-fracture. Ultrastruct. Pathol., 1998, 22:413–20.
CHEN S.C., PELLETIER D.B., AO P., BOYNTON A.L.: Connexin 43 reverses the phenotype of transformed cells and alters cyclin-dependent kinases. Cell Growth Differ. 1995, 6:681–690.
GIEPMANS B.N., MOOLENAAR W.H.: The gap junction protein connexin 43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr. Biol., 1998, 8:931–4.
GRANOT I., DEKEL N.: Developmental expression and regulation of the gap junction protein and transcript in rat ovaries. Mol. Reprod. Dev., 1997, 47:231–9.
HOTZ-WAGENBLATT A., SHALLOWAY D.: Gap junctional communication and neoplastic transformation. Critical Reviews in Oncogenesis, 1993, 5:541–558.
HANNA E.A., UMHAUER S., ROSHONG S.L.,et al.: Gap junctional intercellular communication and connexin 43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro. Carcinogenesis, 1999, 20:1369–73.
HOSSAIN M.Z., JAGDALE A., PENG A.O., LECIEL C., RUO-PAN HUANG, BOYNTON A.L.: Impaired expression and postranslational processing of Connexin43 and downregulation of gap junctional communication in neoplastic human prostate cells. Prostate, 1999, 38:55–59.
JAMIESON S., GOING J.J., D’ARCY R., GEORGE W.D.: Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours. J. Pathol., 1998, 184:37–43.
JOU Y.S., LAYHE B., MATESIC D.F,et al.: Inhibition of gap junctional intercellular communication and malignant transformation of rat liver epithelial cells by neu oncogene. Carcinogenesis, 1995, 16:311–317.
KANEMITSU M.Y., LOO L.W., SIMON S., LAU A.F., ECKHART W.: Tyrosine phosphorylation of connexin 43 by v-Src is mediated by SH2 and SH3 domain interactions. J. Biol. Chem., 1997, 272:22824–22831
KOFFLER L., ROSHONG S., KYU, PARK I.,et al.: Growth inhibition in G(1) and altered expression of cyclin D1 and p27(kip-1) after forced connexin expression in lung and liver carcinoma cells. J. Cell. Biochem., 2000, 79:347–354
KRUTOVSKIKH V.A., TROYANOVKI S.M., PICCOLI C.,et al.: Differential effect of subcellular localization of communication impairing gap junction protein connexin 43 on tumor cell growth in vivo. Oncogene. 2000, 19:505–513.
LABLACK A., BOURDON V., DEFAMIE N.,et al.: Ultrastructural and biochemical evidence for gap junction and connexin 43 expression in a clonal Sertoli cell line: a potential model in the study of junctional complex formation. Cell. Tissue Res. 1998, 294:279–287.
LAMPE P.D., TENBROEK E.M., BURT J.M., KURATA W.E., JOHNSON R.G., LAU A.F.: Phosphorylation of connexin 43 on serine 368 by protein kinase C regulates gap junctional communication. J. Cell. Biol., 2000, 149:1503–1512.
LAU A., KURATA W.E., KANEMITSU M.Y.,et al.: Regulation of connexin 43 function by activated tyroine protein kinases. J. Bioenerg. Biomembr., 1999, 28:359–368.
LEE S.M., TOMASETTO C., SAGER R.: Positive selection of candidate tumor suppressor genes by subsractive hybridization. Proc. Natl. Acad. Sci. USA, 1991, 88:2825–2829.
LEE S.W., TOMASETTO C., PAUL D., KEYOMARSI K., SAGER R.: Transcriptional downregulation of gapjunction proteins blocks junctional communication in human mammary tumor cell lines. J. Cell. Biol., 1992, 118:1213–1221.
LI R., MATHER J.P.: Lindane, an inhibitor of gap junction formation, abolishes oocyte directed follicle organizing activity in vitro. Endocrinology, 1997, 138:4477–4480
McGINLEY D., POSALAKY Z., PORVAZNIK M, RUSSELL L.: Gap junctions between Sertoli cell and germ cells of rat seminiferous tubules. Tissue Cell., 1977, 11:741–754.
NOGUCHI M., NOMATA K., WATANABE J.I., SATO H., KANETAKE H., SAITO Y.: Disruption of gap junctional intercellular communication in human renal cancer cell lines. Urology, 1999, 53:218–222.
PLUM A., HALLAS G MAGIN T.,et al.: Unique and shared functions of different connexins in mice. Curr. Biol., 2000, 10:1083–1091.
REN P., MEHTA P.P., RUCH R.J.: Inhibition of gap junctional intercellular communication by tumor promoters in connexin 43 and connexin 32-expressing liver cells: cell specificity and role of protein kinase C. Carcinogenesis, 1998, 19:169–175.
REAUME A.G., DE SOUSA P.A., KULKARNI Set al.: Cardiac malformation in neonatal mice lacking connexin 43. Science 1995, 267:1831–1834.
RISLEY M.S., TAN I. ROY C., SAEZ J.C.: Cell-age- and stage-dependent distribution of connexin43 gap junctions in testes. J. Cell. Sci., 1992, 103:81–96
SCHLEMMER S.R., NOVOTNY D.B., DAUFMAN D.G.: Changes in connexin 43 protein expression in human endometrial carcinoma. Exp. Mol. Pathol., 1999, 67:150–63.
SIMON A.M., GOODENOUGH D.A., LI E., PAUL D.L.: Female infertility in mice lacking connexin 37. Nature, 1997, 385:525–529
STATUTO M., AUDEBET C.H., TON OLI H., SELMIRUBY S., ROUSSET B., MUNARI-SILEM Y.: Restoration of cell-to-cell communication in thyroid cell lines by tranfectionn with and stable expression of the connexine 32. J. Cell. Biol., 1997, 272, 24710–24716.
STEGER K., TTENS F., BERGMANN M.: Expression of connexin 43 in human testis. Histochem. Cell. Biol., 1999, 112:215–220.
TOYOFUKU T., YABUKI M., OTSU K., KUZUYA T., HORI M., TADA M.: Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J. Biol. Chem. 1998, 273: 12725–12731.
YAMASAKI H., KRUTOVSKIKH V., MESNIL M., TANAKA T., ZAIDAN-DABGLI M.L., OMORI Y.: Role of connexins (gap junction) genes in cell growth control and carcinogenesis. C.R. Acad. Sci. Paris, 1999, 322:1651–1659.
ZHU D., CAVENEY S., KIDDER G.M., NAUS C.G.C.: Transfection of C6 glioma cells with Connexin 43 cDNA: Analysis of expression, intercellular coupling, and cell proliferation. Proc. Natl. Acad. Sci USA, 1991, 88:1883–1887.
Author information
Authors and Affiliations
Additional information
Communication orale sélectionnées au XVIIème Congrès de la SALF, 7-8 décembre 2000, Bordeaux.
Rights and permissions
About this article
Cite this article
Roger, C., Mograbi, B., Chevallier, D. et al. Localisation aberrante de la connexine 43 dans le cancer du testicule. Androl. 11, 56–62 (2001). https://doi.org/10.1007/BF03034395
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03034395
Mots clés
- cancer testiculaire
- séminome
- communication jonctionnelle intercellulaire par gap
- suppresseur tumoral
- connexine 43