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TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.
J Cell Physiol. 2008 Dec; 217(3):759-68.JC

Abstract

One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

Authors+Show Affiliations

INSERM U697, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18668519

Citation

Tacheau, Charlotte, et al. "TGF-beta Induces Connexin43 Gene Expression in Normal Murine Mammary Gland Epithelial Cells Via Activation of P38 and PI3K/AKT Signaling Pathways." Journal of Cellular Physiology, vol. 217, no. 3, 2008, pp. 759-68.
Tacheau C, Fontaine J, Loy J, et al. TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways. J Cell Physiol. 2008;217(3):759-68.
Tacheau, C., Fontaine, J., Loy, J., Mauviel, A., & Verrecchia, F. (2008). TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways. Journal of Cellular Physiology, 217(3), 759-68. https://doi.org/10.1002/jcp.21551
Tacheau C, et al. TGF-beta Induces Connexin43 Gene Expression in Normal Murine Mammary Gland Epithelial Cells Via Activation of P38 and PI3K/AKT Signaling Pathways. J Cell Physiol. 2008;217(3):759-68. PubMed PMID: 18668519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways. AU - Tacheau,Charlotte, AU - Fontaine,Juliette, AU - Loy,Jennifer, AU - Mauviel,Alain, AU - Verrecchia,Franck, PY - 2008/8/1/pubmed PY - 2008/10/17/medline PY - 2008/8/1/entrez SP - 759 EP - 68 JF - Journal of cellular physiology JO - J Cell Physiol VL - 217 IS - 3 N2 - One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/18668519/TGF_beta_induces_connexin43_gene_expression_in_normal_murine_mammary_gland_epithelial_cells_via_activation_of_p38_and_PI3K/AKT_signaling_pathways_ L2 - https://doi.org/10.1002/jcp.21551 DB - PRIME DP - Unbound Medicine ER -