By a News Reporter-Staff News Editor at Cancer Weekly -- Investigators publish new report on Oncology. According to news reporting originating from Pingtung, Taiwan, by NewsRx correspondents, research stated, "Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype."
Our news editors obtained a quote from the research from the National Pingtung University of Science and Technology, "However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that gamma-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABA(A)R alpha(1) and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R alpha(1)-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R alpha(1) immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABA(A)R alpha(1) immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands."
According to the news editors, the research concluded: "These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression."
For more information on this research see: Linking gamma-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer. Molecular and Cellular Endocrinology, 2014;383(1-2):69-79. Molecular and Cellular Endocrinology can be contacted at: Elsevier Ireland Ltd, Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland. (Elsevier - www.elsevier.com; Molecular and Cellular Endocrinology - www.elsevier.com/wps/product/cws_home/506028)
The news editors report that additional information may be obtained by contacting W.J. Wu, Natl Pingtung Univ Sci & Technol, Dept. of Food Sci, Pingtung 91207, Taiwan. Additional authors for this research include Q. Yang, K.M. Fung, M.R. Humphreys, L.S. Brame, A. Cao, Y.T. Fang, P.T. Shih, B.P. Kropp and H.K. Lin (see also Oncology).
Keywords for this news article include: Asia, Taiwan, Pingtung, Oncology, Amino Acids, Prostate Cancer, Protein Kinases, Membrane Proteins, Peptide Receptors, Aminobutyric Acids, Phosphotransferases, Prostatic Neoplasms, Epidermal Growth Factor Receptor, Receptor Protein-Tyrosine Kinases, Gastrointestinal Hormone Receptors
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