This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holder, J. W. Articles by Barrett, J. C. Search for Related Content PubMed PubMed Citation Articles by Holder, J. W. Articles by Barrett, J. C.

Gap Junction Function and Cancer

Genetic Toxicology Assessment Branch, Office of Health and Environmental Assessment, Office of Research and Development (RD-689), EPA, Washington, DC 20460 [J. W. H.]; National Institute for the Advancement of in Vitro Sciences, Irvine, California 92715 [E. E.]; and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [J. C. B.]

Gap junctions (GJs) provide cell-to-cell communication of essential metabolites and ions. GJs allow tissues to average responses, clear waste products, and minimize the effects of xenobiotics by dilution and allowing steady-state catabolism. Many chemicals can adversely affect the membrane GJ assembly causing reversible alterations in GJ intercellular communication. During toxicity essential metabolites, ions, and regulators are not shared homeostatically throughout a tissue community. Alterations in metabolic circuits are thought to interrupt organ integration. Persistent GJ perturbation can cause chronic effects (e.g., cancer), and many tumor promoters inhibit GJ intercellular communication. Liver precancerous foci intracommunicate (but at a reduced level) and intercommunicate improperly (or not at all) across the foci boundary to normal cells. In time, foci can become less regulated and more isolated within the tissue. GJs remain reduced quantitatively in the tumor progression stage and may be qualitatively altered in metastasis since connections are made between the primary tumor cells and foreign host cells at the secondary metastatic site. Cell sorting and binding mechanisms by the cell adhesion molecules and integrins may also be altered at secondary sites. This may allow the relocation of primary tumor cells and nurturance via GJs at the secondary site.

¹ The views expressed in this paper are those of the authors and do reflect the views or policies of the United States Environmental Protection Agency or the National Institute of Environmental Health Sciences.

² To whom requests for reprints should be addressed, at Genetic Toxicology Assessment Branch, Office of Health and Environmental Assessment, Office of Research and Development (RD-689), United States Environmental Protection Agency, Washington, DC 20460.

Received 12/18/92. Accepted 5/26/93.

This article has been cited by other articles:

				H.-Z. Wang, P. R. Brink, and G. J. Christ Gap junction channel activity in short-term cultured human detrusor myocyte cell pairs: gating and unitary conductances Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1366 - C1376. [Abstract] [Full Text] [PDF]

				P. Tanmahasamut and N. Sidell Up-Regulation of Gap Junctional Intercellular Communication and Connexin43 Expression by Retinoic Acid in Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4151 - 4156. [Abstract] [Full Text] [PDF]

				E. G. A. Harks, P. H. J. Peters, J. L. J. van Dongen, E. J. J. van Zoelen, and A. P. R. Theuvenet Autocrine production of prostaglandin F2{alpha} enhances phenotypic transformation of normal rat kidney fibroblasts Am J Physiol Cell Physiol, July 1, 2005; 289(1): C130 - C137. [Abstract] [Full Text] [PDF]

				E. Leithe and E. Rivedal Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43 J. Cell Sci., March 1, 2004; 117(7): 1211 - 1220. [Abstract] [Full Text] [PDF]

				E. Leithe, V. Cruciani, T. Sanner, S.-O. Mikalsen, and E. Rivedal Recovery of gap junctional intercellular communication after phorbol ester treatment requires proteasomal degradation of protein kinase C Carcinogenesis, July 1, 2003; 24(7): 1239 - 1245. [Abstract] [Full Text] [PDF]

				T. Husoy, V. Cruciani, H. K. Knutsen, S.-O. Mikalsen, H. B. Olstorn, and J. Alexander Cells heterozygous for the ApcMin mutation have decreased gap junctional intercellular communication and connexin43 level, and reduced microtubule polymerization Carcinogenesis, April 1, 2003; 24(4): 643 - 650. [Abstract] [Full Text] [PDF]

				J. K. Chipman, A. Mally, and G. O. Edwards Disruption of Gap Junctions in Toxicity and Carcinogenicity Toxicol. Sci., February 1, 2003; 71(2): 146 - 153. [Abstract] [Full Text] [PDF]

				N. Provost, M. Moreau, A. Leturque, and C. Nizard Ultraviolet A radiation transiently disrupts gap junctional communication in human keratinocytes Am J Physiol Cell Physiol, January 1, 2003; 284(1): C51 - C59. [Abstract] [Full Text] [PDF]

				A. T. Grazul-Bilska, L. P. Reynolds, J. J. Bilski, and D. A. Redmer Effects of Second Messengers on Gap Junctional Intercellular Communication of Ovine Luteal Cells Throughout the Estrous Cycle Biol Reprod, September 1, 2001; 65(3): 777 - 783. [Abstract] [Full Text] [PDF]

				E. Kievit, M. K. Nyati, E. Ng, L. D. Stegman, J. Parsels, B. D. Ross, A. Rehemtulla, and T. S. Lawrence Yeast Cytosine Deaminase Improves Radiosensitization and Bystander Effect by 5-Fluorocytosine of Human Colorectal Cancer Xenografts Cancer Res., December 1, 2000; 60(23): 6649 - 6655. [Abstract] [Full Text]

				S.-H. Jeong, S. S. M. Habeebu, and C. D. Klaassen Cadmium Decreases Gap Junctional Intercellular Communication in Mouse Liver Toxicol. Sci., September 1, 2000; 57(1): 156 - 166. [Abstract] [Full Text] [PDF]

				M Hsu, T Andl, G Li, J. Meinkoth, and M Herlyn Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression J. Cell Sci., January 5, 2000; 113(9): 1535 - 1542. [Abstract] [PDF]

				A. J. Mao, J. Bechberger, D. Lidington, J. Galipeau, D. W. Laird, and C. C. G. Naus Neuronal Differentiation and Growth Control of Neuro-2a Cells After Retroviral Gene Delivery of Connexin43 J. Biol. Chem., October 27, 2000; 275(44): 34407 - 34414. [Abstract] [Full Text] [PDF]