This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schroeder, M. D. Articles by Schuler, L. A. Search for Related Content PubMed PubMed Citation Articles by Schroeder, M. D. Articles by Schuler, L. A.

Inhibition of Prolactin (PRL)-Induced Proliferative Signals in Breast Cancer Cells by a Molecular Mimic of Phosphorylated PRL, S179D-PRL

Department of Comparative Biosciences (M.D.S., J.L.B., L.A.S.), University of Wisconsin, Madison, Wisconsin 53706; and Division of Biomedical Sciences (A.M.W.), University of California, Riverside, California 92521

Address all correspondence and requests for reprints to: Dr. Linda A. Schuler, Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, Wisconsin 53706. E-mail: schulerl{at}svm.vetmed.wisc.edu.

Posttranslational modifications of prolactin (PRL), including phosphorylation, vary with physiologic state and alter biologic activity. In light of the growing evidence for a role for PRL in proliferation in mammary cancer, we examined the ability of a mimic of phosphorylated human PRL, S179D-PRL, to initiate signals to several pathways in mammary tumor cells alone and in combination with unmodified PRL. Unmodified PRL employed multiple pathways to increase cellular proliferation and cyclin D1 levels in PRL-deficient MCF-7 cells. S179D-PRL was a weak agonist compared with unmodified PRL with regard to cellular proliferation, cyclin D1 levels, and phosphorylation of signal transducer and activator of transcription 5 and ERKs. However, S179D-PRL was a potent antagonist of unmodified PRL to these endpoints. In contrast to the reduced levels of the long isoform of the PRL receptor observed in response to a 3-d incubation with unmodified PRL, S179D-PRL up-regulated expression of this isoform, 4-fold. These studies support the utility of this mutant as a PRL antagonist to proliferative signals in mammary epithelial cells, including a potential role in breast cancer therapeutics.

This article has been cited by other articles:

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				B C Nephew, J Amico, H M Cai, A M Walker, and R S Bridges Intracerebroventricular administration of the prolactin (PRL) receptor antagonist, S179D PRL, disrupts parturition in rats Reproduction, July 1, 2007; 134(1): 155 - 160. [Abstract] [Full Text] [PDF]

				E. K. Ueda, H.-L. Lo, P. Bartolini, and A. M. Walker S179D Prolactin Primarily Uses the Extrinsic Pathway and Mitogen-Activated Protein Kinase Signaling to Induce Apoptosis in Human Endothelial Cells Endocrinology, October 1, 2006; 147(10): 4627 - 4637. [Abstract] [Full Text] [PDF]

				E. Ueda, U. Ozerdem, Y.-H. Chen, M. Yao, K. T. Huang, H. Sun, M. Martins-Green, P. Bartolini, and A. M Walker A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone. Endocr. Relat. Cancer, March 1, 2006; 13(1): 95 - 111. [Abstract] [Full Text] [PDF]

				Z. Nouhi, N. Chughtai, S. Hartley, E. Cocolakis, J.-J. Lebrun, and S. Ali Defining the Role of Prolactin as an Invasion Suppressor Hormone in Breast Cancer Cells Cancer Res., February 1, 2006; 66(3): 1824 - 1832. [Abstract] [Full Text] [PDF]

				W. Wu, E. Ginsburg, B. K. Vonderhaar, and A. M. Walker S179D Prolactin Increases Vitamin D Receptor and p21 through Up-regulation of Short 1b Prolactin Receptor in Human Prostate Cancer Cells Cancer Res., August 15, 2005; 65(16): 7509 - 7515. [Abstract] [Full Text] [PDF]

				J. H. Gutzman, S. E. Nikolai, D. E. Rugowski, J. J. Watters, and L. A. Schuler Prolactin and Estrogen Enhance the Activity of Activating Protein 1 in Breast Cancer Cells: Role of Extracellularly Regulated Kinase 1/2-Mediated Signals to c-fos Mol. Endocrinol., July 1, 2005; 19(7): 1765 - 1778. [Abstract] [Full Text] [PDF]

				M. J. Naylor, S. R. Oakes, M. Gardiner-Garden, J. Harris, K. Blazek, T. W. C. Ho, F. C. Li, D. Wynick, A. M. Walker, and C. J. Ormandy Transcriptional Changes Underlying the Secretory Activation Phase of Mammary Gland Development Mol. Endocrinol., July 1, 2005; 19(7): 1868 - 1883. [Abstract] [Full Text] [PDF]

				V. Goffin, S. Bernichtein, P. Touraine, and P. A. Kelly Development and Potential Clinical Uses of Human Prolactin Receptor Antagonists Endocr. Rev., May 1, 2005; 26(3): 400 - 422. [Abstract] [Full Text] [PDF]

				D. Tan, D. A. Johnson, W. Wu, L. Zeng, Y. H. Chen, W. Y. Chen, B. K. Vonderhaar, and A. M. Walker Unmodified Prolactin (PRL) and S179D PRL-Initiated Bioluminescence Resonance Energy Transfer between Homo- and Hetero-Pairs of Long and Short Human PRL Receptors in Living Human Cells Mol. Endocrinol., May 1, 2005; 19(5): 1291 - 1303. [Abstract] [Full Text] [PDF]

				J. H. Gutzman, D. E. Rugowski, M. D. Schroeder, J. J. Watters, and L. A. Schuler Multiple Kinase Cascades Mediate Prolactin Signals to Activating Protein-1 in Breast Cancer Cells Mol. Endocrinol., December 1, 2004; 18(12): 3064 - 3075. [Abstract] [Full Text] [PDF]