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AMEAE M. WALKER, PH.D.

Professor of Biomedical Sciences
Ph.D., Liverpool University, England
Postdoctorate, Yale University

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Research Summary

Research in my laboratory is concerned with the growth factor activities of the hormone prolactin. These growth factor activities occur in many tissues including the pituitary, breast, endocrine pancreas, liver, prostate, and cells of the immune system. Although most prolactin is produced by the pituitary, some is produced in these other tissues where it may act as an autocrine or paracrine growth factor. In four of these tissues we have demonstrated antagonism between unmodified and phosphorylated prolactin in the regulation of growth, an antagonism which can be disturbed, leading to abnormal cell proliferation. In the case of the prostate, we have demonstrated that a molecular mimic of phosphorylated prolactin effectively inhibits metastases and growth of the primary tumor of late stage human prostate cancer cells in an animal model. Other projects include effects of the molecular mimic on the development and progression of breast cancer and pituitary tumors. Thus we investigate the posttranslational modification of prolactin, the regulation of prolactin release, prolactin-receptor interactions, signal transduction and effects on gene transcription in each of these tissues. The laboratory uses a wide spectrum of techniques ranging from microscopy to molecular biology to whole animal physiology, each of which may be applied to answer a particular question.
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Publications

Yang L, Kuo CB, Liu Y, Coss D, Xu X, Chen C, Oster-Granite ML, Walker AM. Administration of unmodified prolactin (U-PRL) and a molecular mimic of phosphorylated prolactin (PP-PRL) during rat pregnancy provides evidence that the U-PRL:PP-PRL ratio is crucial to the normal development of pup tissues. J Endocrinol 168: 227-238, 2001.

Bridges RS, Rigero BA, Byrnes EM, Yang L, Walker AM. Central infusions of the recombinant human prolactin receptor antagonist, S179D PRL, delays the onset of maternal behavior in steroid-primed, nulliparous female rats. Endocrinology 142: 730-739, 2001.

Warner MD, Walker AM, D'Souza DC, Lee D, Nasseri D, Peabody CA. Lower prolactin bioactivity in unmedicated schizophrenic patients.Psychiatry Res 102: 249-254, 2001.

Lorenson MY, Walker AM. Structure-function relationships in prolactin. In: Horseman ND, ed. Prolactin. Norwell, Massachusetts, Kluwer Academic Press 189-217, 2001.

Xu X, Kreye E, Kuo CB, Walker AM. A molecular mimic of phosphorylated prolactin markedly reduced tumor incidence and size when DU145 human prostate cancer cells were grown in nude mice. Cancer Res 61: 6098-6104, 2001.

Walker AM. Unmodified and phosphorylated prolactin and gamma delta T cell development and function. Lupus 10: 735-741, 2001.

Tuazon, PT, Lorenson MY, Walker, AM, Traugh JA. p21-Activated protein kinase gamma-PAK in pituitary secretory granules phosphorylates prolactin. FEBS Letters 515: 84-88, 2002.

Kuo CB, Wu W, Xu X, Yang L, Chen C, Coss D, Birdsall B,Nasseri D, Walker AM Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes -casein gene expression in the rat mammary gland. Cell and Tissue Research 309: 429-437, 2002.

Budge H, Mostyn A, Wilson V, Khong A, Walker AM, Symonds ME, Stephenson T. The effect of maternal prolactin infusion during pregnancy on fetal adipose tissue development. J. Endocrinol. 174: 427-233, 2002.

Yang L, Lii S, Kuo B, Buckley A, Buckley D, Chen C, Xu X, Coss, D and Walker AM Maternal prolactin composition can permanently affect epidermal T cell function in the offspring. Developmental and Comparative Immunology 26: 849-860, 2002.

Xu X, Wu W, Williams V, Deng C, Khong A, Chen Y-H, Walker AM. Opposite effects of unmodified PRL and a molecular mimic of phosphorylated PRL on morphology and the expression of prostate-specific genes in the normal rat prostate. The Prostate 54: 25-33, 2003.

Johnson TE, Vue M, Brekhus S, Khong A, Ho TWC, Walker AM. Unmodified prolactin (PRL) promotes PRL secretion and acidophil hypertrophy and is associated with pituitary hyperplasia in female rats. Endocrine 20: 101-110, 2003.

Schroeder MD, Brockman JL, Walker AM, Schuler LA. Inhibition of prolactin (PRL)-induced proliferative signals in breast cancer cells by a molecular mimic of phosphorylated PRL, S179D-PRL. Endocrinology 144: 5300-5307, 2003.

Wu W, Coss D, Lorenson MY, Kuo CB, Xu X, Walker AM. Different biological effects of unmodified prolactin and a molecular mimic of phosphorylated prolactin involve different signaling pathways. Biochemistry 42: 7561-7570, 2003.

Huang KT, Chen YH, Walker AM. Inaccuracies in MTS assays: major distorting effects of medium, serum albumin, and fatty acids. Biotechniques 37: 406-412, 2004.

Pearce S, Budge H, Mostyn A, Generver E, Webb R, Ingleton P, Walker AM, Symonds ME, Stephenson T. Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep. J. Endocrinol. 184: 351-359, 2005.

Tan D, Johnson DA, Wu W, Zeng L, Chen YH, Chen WY, Vonderhaar BK, Walker AM. Unmodified prolactin (PRL) and S179D PRL-initiated bioluminescence resonance energy transfer between homo- and hetero-pairs of long and short PRL receptors in living human cells. Mol Endocrinol. 19: 1291-1303, 2005.

Naylor MJ, Oakes SR, Gardiner-Garden M, Harris J, Blazek K, Ho TWC, Li FC, Wynick D, Walker AM, Ormandy CJ. Transcriptional changes underlying the secretory activation phase of mammary gland development. Mol Endocrinol. 19: 1868-1883, 2005.

Wu W, Ginsburg E, Vonderhaar BK, Walker AM. S179D prolactin increases vitamin D receptor and p21 through upregulation of short 1b prolactin receptor in human prostate cancer cells. Cancer Research 65 (16) in press, 2005.

Wu W, Walker AM. Human chorionic gonadotropin β (HCGβ) downregulates E-cadherin and promotes prostate cancer cell migration and invasion. Cancer. in press, 2005.

Walker AM. Prolactin Receptor Antagonists. Current Opin Investigational Drugs 6: 378-385, 2005.
 

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