Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.

This article has been cited by other articles:

				A. D. Gultice, K. Kulkarni-Datar, and T. L. Brown Hypoxia-Inducible Factor 1alpha (HIF1A) Mediates Distinct Steps of Rat Trophoblast Differentiation in Gradient Oxygen Biol Reprod, January 1, 2009; 80(1): 184 - 193. [Abstract] [Full Text] [PDF]

				Q. A. Winger, J. Guttormsen, H. Gavin, and F. Bhushan Heat Shock Protein 1 and the Mitogen-Activated Protein Kinase 14 Pathway Are Important for Mouse Trophoblast Stem Cell Differentiation Biol Reprod, May 1, 2007; 76(5): 884 - 891. [Abstract] [Full Text] [PDF]

				R.P. Webster, D. Brockman, and L. Myatt Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia Mol. Hum. Reprod., November 1, 2006; 12(11): 677 - 685. [Abstract] [Full Text] [PDF]

				A. D. Gultice, K. L. Selesniemi, and T. L. Brown Hypoxia Inhibits Differentiation of Lineage-Specific Rcho-1 Trophoblast Giant Cells Biol Reprod, June 1, 2006; 74(6): 1041 - 1050. [Abstract] [Full Text] [PDF]

				I. Knerr, B. Huppertz, C. Weigel, J. Dotsch, C. Wich, R.L. Schild, M.W. Beckmann, and W. Rascher Endogenous retroviral syncytin: compilation of experimental research on syncytin and its possible role in normal and disturbed human placentogenesis Mol. Hum. Reprod., August 1, 2004; 10(8): 581 - 588. [Abstract] [Full Text] [PDF]

				A H K El-Hashash and S J Kimber Trophoblast differentiation in vitro: establishment and characterisation of a serum-free culture model for murine secondary trophoblast giant cells Reproduction, July 1, 2004; 128(1): 53 - 71. [Abstract] [Full Text] [PDF]

				A.-M. Bamberger, C. M. Bamberger, S. Aupers, K. Milde-Langosch, T. Loning, and A. Makrigiannakis Expression pattern of the activating protein-1 family of transcription factors in the human placenta Mol. Hum. Reprod., April 1, 2004; 10(4): 223 - 228. [Abstract] [Full Text] [PDF]

				D. O. Wiemers, L.-j. Shao, R. Ain, G. Dai, and M. J. Soares The Mouse Prolactin Gene Family Locus Endocrinology, January 1, 2003; 144(1): 313 - 325. [Abstract] [Full Text] [PDF]

				T. Kamei, S. R. Jones, B. M. Chapman, K. L. MCGonigle, G. Dai, and M. J. Soares The Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Modulates the Endocrine Differentiation of Trophoblast Cells Mol. Endocrinol., July 1, 2002; 16(7): 1469 - 1481. [Abstract] [Full Text] [PDF]