Autocrine/paracrine regulation of breast cancer cell proliferation by growth hormone releasing hormone via Ras, Raf, and mitogen-activated protein kinase

Molecular Endocrinology
G SiriwardanaP Zeitler

Abstract

Although GHRH has previously been shown to regulate proliferation of breast cancer cells and prevent apoptosis, the intracellular pathways mediating this effect have not been clarified. Exogenous GHRH stimulated a dose-dependent proliferative response within 24 h in MDA-231, as well as in T47D cells and in MCF-7 cells transfected with the GHRH receptor. The proliferation of MDA-MB-231 (MDA-231) cells was associated with an increase in tritiated thymidine uptake. In addition, phosphorylation of MAPK was rapidly stimulated by GHRH. The phosphorylation of MAPK by GHRH was prevented by transfection of the cells with dominant-negative Ras or Raf or by pretreatment of cells with Raf kinase 1 inhibitor. The inhibition of Ras and Raf, as well as the inhibition of MAPK phosphorylation by PD98059, also prevented GHRH-induced cell proliferation. Finally, pretreatment of cells with the somatostatin analog, BIM23014, also prevented GHRH-induced MAPK phosphorylation and cell proliferation. These results indicate that GHRH stimulates dose-dependent cell proliferation of MDA-231 breast cancer cells through a pathway that requires Ras, Raf, and MAPK phosphorylation. The results also provide support for a possible autocrine/paracrine antagonism ...Continue Reading

Citations

Dec 18, 2009·Molecules and Cells·Younghee AhnCheolju Lee
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nektarios Barabutis, Andrew V Schally
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ferenc G RickStephan Seitz
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nektarios BarabutisHippokratis Kiaris
Dec 17, 2009·Cellular and Molecular Life Sciences : CMLS·Agnieszka SiejkaNektarios Barabutis
Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yong Jie QinChi Pui Pang
Mar 1, 2008·Molecular and Cellular Endocrinology·Heather L WattUjendra Kumar
Aug 28, 2007·Pharmacology & Therapeutics·Davide Cervia, Paola Bagnoli
Feb 18, 2010·International Journal of Cancer. Journal International Du Cancer·Eva PozsgaiSzabolcs Bellyei
Jun 4, 2010·Journal of Cellular and Molecular Medicine·Nektarios BarabutisAndrew V Schally
Feb 13, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Qunchao MaHong Yu
Jul 10, 2021·Molecular and Cellular Endocrinology·Yurong Zheng, Antoine E Karnoub

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis