Recent studies show that gastrointestinal hormones/growth factors may stimulate cell growth by stimulating multiple intracellular tyrosine phosphorylation (TyrP) signaling cascades as well as by transactivating growth factor receptors. However at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades. Our studies have been in two general areas, which include studies of intracellular signaling cascades primarily by tyrosine kinases and studies of tumoral growth attempting to develop novel agents for growth inhibition. Recent studies show that gastrointestinal hormones, similar to growth factors, may stimulate cell growth/cell signaling by stimulating multiple intracellular tyrosine phosphorylation (TyrP) cascades. Whereas these cascades have been extensively investigated with growth factors, little is known in this area with may gastrointestinal hormones. The goal of these studies is to clarify this area primarily concentrating on cholecystokinin receptor cascades and bombesin receptor activation using primarily pancreatic acini as a model natural cell system as well as to study the role of gastrointestinal hormones in stimulating tumor growth(primarily lung cancer ). In four different studies activation of Bn-related receptors (BRS-3) as well as PACAP receptors on lung cancer cells were found to stimulate tumor growth and the mechanism involved transactivation of the EGF receptor as well as stimulating activation of p125FAK, paxillin and PYK2 in addition to activation of reactive oxygen species, matrix metalloproteinases and Src. In pancreatic acini, CCK and other PLC activating hormones was shown to activate the Src kinase YES and its activation to play an important role in activating other key signaling cascades stimulated by CCK. In collaboration with Prof Ito, Fukuoka, Japan, cytosolic double-stranded DNA was shown to show a damage-associated molecular patten that induced the inflammatory response in pancreatic stellate cells and to be a plausible mechanism for tissue injury-associated pancreatitis. .

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Ramos-Alvarez, Irene; Jensen, R T (2018) P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades. Am J Physiol Gastrointest Liver Physiol 315:G302-G317
Moreno, Paola; Mantey, Samuel A; Lee, Suk H et al. (2018) A possible new target in lung-cancer cells: The orphan receptor, bombesin receptor subtype-3. Peptides 101:213-226
Moody, Terry W; Ramos-Alvarez, Irene; Jensen, Robert T (2018) Neuropeptide G Protein-Coupled Receptors as Oncotargets. Front Endocrinol (Lausanne) 9:345
Moreno-Villegas, Zaida; Martín-Duce, Antonio; Aparicio, César et al. (2018) Activation of bombesin receptor Subtype-3 by [D-Tyr6,?-Ala11,Phe13,Nle14]bombesin6-14 increased glucose uptake and lipogenesis in human and rat adipocytes. Mol Cell Endocrinol 474:10-19
Moody, Terry W; Ramos-Alvarez, Irene; Moreno, Paula et al. (2017) Endothelin causes transactivation of the EGFR and HER2 in non-small cell lung cancer cells. Peptides 90:90-99
Lee, Lingaku; Ito, Tetsuhide; Nakamura, Taichi et al. (2017) Antifibrotic Effect of Saturated Fatty Acids via Endoplasmic Reticulum Stress Response in Rat Pancreatic Stellate Cells. Pancreas 46:385-394
Ito, Tetsuhide; Jensen, Robert T (2017) Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 24:15-24
Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T (2016) The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events. Biochim Biophys Acta 1862:1122-36
Ito, Tetsuhide; Lee, Lingaku; Jensen, Robert T (2016) Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies. Expert Opin Pharmacother 17:2191-2205
Ramos-Álvarez, Irene; Nakamura, Taichi; Mantey, Samuel A et al. (2016) Novel chiral-diazepines function as specific, selective receptor agonists with variable coupling and species variability in human, mouse and rat BRS-3 receptor cells. Peptides 75:8-17

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