This Article Full Text 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 Caristi, S. Articles by Weisz, A. Search for Related Content PubMed PubMed Citation Articles by Caristi, S. Articles by Weisz, A.

Estrogens Do Not Modify MAP Kinase-dependent Nuclear Signaling during Stimulation of Early G₁ Progression in Human Breast Cancer Cells¹

Dipartimento di Patologia generale, Seconda Università degli Studi di Napoli, 80138 Napoli [S. Car., J. L. G., F. M., M. I., S. Cap., M. C., L. A., L. C., F. B., A. W.], and Dipartimento di Patologia e Microbiologia sperimentale, Università degli Studi di Messina, 98125 Messina [D. T.], Italy

Estrogens are direct mitogens for hormone-responsive human breast cancercells, where they promote cell cycle progression and induce transcriptionalactivation of "immediate early" and cyclin genes. Nongenomic signalingby estrogens, including rapid changes of mitogen-activated protein(MAP) kinase and other signal-transduction-cascades activity, has beenproposed to be essential for the mitogenic actions of these hormones and their nuclear receptors. Because regulation of gene transcription is considered a key step in cell cycle control by mitogenic protein kinase cascades, here we investigated the possibility that estrogen might induce the activation of extracellular signal-regulated kinase (Erk) 1/2-, c-Jun NH₂-terminal kinase-, p38- or protein kinase A-responsive transcription factors in the cell nucleus during stimulation of early G₁ progression, a timing coincident with the maximum effects of these hormones on such enzyme activity. No significant changes in protein kinase-mediated transcription factor activity could be detected here after estrogen stimulation of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb phosphorylation, all key events in cell cycle stimulation by mitogens, even in the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase (Mek)1/2 inhibitor. Thus, estrogens do not appear to convey significant protein kinase-dependent signaling to the cell nucleus during the early phases of human breast cancer cell stimulation. Furthermore, hormonal regulation of G₁ gene transcription can occur even without additional activation of the Mek-Erk1/2 pathway by estrogen receptors.

This article has been cited by other articles:

				A. Zheng, A. Kallio, and P. Harkonen Tamoxifen-Induced Rapid Death of MCF-7 Breast Cancer Cells Is Mediated via Extracellularly Signal-Regulated Kinase Signaling and Can Be Abrogated by Estrogen Endocrinology, June 1, 2007; 148(6): 2764 - 2777. [Abstract] [Full Text] [PDF]

				E. J. Filardo, C. T. Graeber, J. A. Quinn, M. B. Resnick, D. Giri, R. A. DeLellis, M. M. Steinhoff, and E. Sabo Distribution of GPR30, a Seven Membrane-Spanning Estrogen Receptor, in Primary Breast Cancer and its Association with Clinicopathologic Determinants of Tumor Progression. Clin. Cancer Res., November 1, 2006; 12(21): 6359 - 6366. [Abstract] [Full Text] [PDF]

				E Horner-Glister, M Maleki-Dizaji, C J Guerin, S M Johnson, J Styles, and I N H White Influence of oestradiol and tamoxifen on oestrogen receptors-{alpha} and -{beta} protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells J. Mol. Endocrinol., December 1, 2005; 35(3): 421 - 432. [Abstract] [Full Text] [PDF]

				X. Zhao, H. Lorenc, H. Stephenson, Y. J. Wang, D. Witherspoon, B. Katzenellenbogen, D. Pfaff, and N. Vasudevan Thyroid hormone can increase estrogen-mediated transcription from a consensus estrogen response element in neuroblastoma cells PNAS, March 29, 2005; 102(13): 4890 - 4895. [Abstract] [Full Text] [PDF]

				A.-M. Gaben, C. Saucier, M. Bedin, G. Redeuilh, and J. Mester Mitogenic Activity of Estrogens in Human Breast Cancer Cells Does Not Rely on Direct Induction of Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase or Phosphatidylinositol 3-Kinase Mol. Endocrinol., November 1, 2004; 18(11): 2700 - 2713. [Abstract] [Full Text] [PDF]

				R. I. Fernando and J. Wimalasena Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt Mol. Biol. Cell, July 1, 2004; 15(7): 3266 - 3284. [Abstract] [Full Text] [PDF]

				V. Marsaud, A. Gougelet, S. Maillard, and J.-M. Renoir Various Phosphorylation Pathways, Depending on Agonist and Antagonist Binding to Endogenous Estrogen Receptor {alpha} (ER{alpha}), Differentially Affect ER{alpha} Extractability, Proteasome-Mediated Stability, and Transcriptional Activity in Human Breast Cancer Cells Mol. Endocrinol., October 1, 2003; 17(10): 2013 - 2027. [Abstract] [Full Text] [PDF]

				M. Marino, F. Acconcia, and A. Trentalance Biphasic Estradiol-induced AKT Phosphorylation Is Modulated by PTEN via MAP Kinase in HepG2 Cells Mol. Biol. Cell, June 1, 2003; 14(6): 2583 - 2591. [Abstract] [Full Text] [PDF]

				S. F. Doisneau-Sixou, P. Cestac, S. Chouini, J. S. Carroll, A. D. Hamilton, S. M. Sebti, M. Poirot, P. Balaguer, J.-C. Faye, R. L. Sutherland, et al. Contrasting Effects of Prenyltransferase Inhibitors on Estrogen-Dependent Cell Cycle Progression and Estrogen Receptor-Mediated Transcriptional Activity in MCF-7 Cells Endocrinology, March 1, 2003; 144(3): 989 - 998. [Abstract] [Full Text] [PDF]

				J. Vondracek, A. Kozubik, and M. Machala Modulation of Estrogen Receptor-Dependent Reporter Construct Activation and G0/G1-S-Phase Transition by Polycyclic Aromatic Hydrocarbons in Human Breast Carcinoma MCF-7 Cells Toxicol. Sci., December 1, 2002; 70(2): 193 - 201. [Abstract] [Full Text] [PDF]

				T. M. Ahola, N. Alkio, T. Manninen, and T. Ylikomi Progestin and G Protein-Coupled Receptor 30 Inhibit Mitogen-Activated Protein Kinase Activity in MCF-7 Breast Cancer Cells Endocrinology, December 1, 2002; 143(12): 4620 - 4626. [Abstract] [Full Text] [PDF]

				S. Zervou, E. Karteris, E.W. Hillhouse, and R.W. Old Steroids mediate the expression of cytoplasmic and membrane-linked components in human myometrial cells Mol. Hum. Reprod., July 1, 2002; 8(7): 597 - 605. [Abstract] [Full Text] [PDF]

				E. K. Lobenhofer, L. Bennett, P. L. Cable, L. Li, P. R. Bushel, and C. A. Afshari Regulation of DNA Replication Fork Genes by 17{beta}-Estradiol Mol. Endocrinol., June 1, 2002; 16(6): 1215 - 1229. [Abstract] [Full Text] [PDF]