Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1

The Journal of Biological Chemistry
T F McGuireC S Johnson

Abstract

Vitamin D(3) inhibits cell growth and induces apoptosis in several human cancer lines in vitro and in vivo. However, little is known about the molecular events involved in vitamin D(3)-induced apoptosis. Here, we demonstrate that the growth-promoting/pro-survival signaling molecule mitogen-activated protein kinase kinase (MEK) is cleaved in a caspase-dependent manner in murine squamous cell carcinoma (SCC) cells induced to undergo apoptosis by treatment with vitamin D(3). Cleavage resulted in nearly complete loss of full-length MEK and ERK1/2 phosphorylation. ERK1/2 expression was affected only slightly. The phosphorylation and expression of Akt, a kinase regulating a second cell survival pathway, was also inhibited after treatment with vitamin D(3). However, the pro-apoptotic signaling molecule MEKK-1 was up-regulated in both apoptotic and non-apoptotic cells with greater induction and partial N-terminal proteolysis of MEKK-1 observed in apoptotic cells. In contrast to vitamin D(3), cisplatin and etoposide down-regulated Akt levels only modestly, did not promote significant loss of MEK expression, and did not up-regulate MEKK-1. We propose that vitamin D(3) induces apoptosis in SCC cells by a unique mechanism involving selecti...Continue Reading

Associated Clinical Trials

Aug 25, 2017·Donald Trump, MD, Donald Trump, MD

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Citations

May 27, 2005·Cancer Chemotherapy and Pharmacology·Josephia R MuindiDonald L Trump
Sep 17, 2002·Urology·Candace S JohnsonDonald L Trump
Aug 28, 2007·Nature Reviews. Cancer·Kristin K DeebCandace S Johnson
Aug 14, 2002·The British Journal of Dermatology·J E Osborne, P E Hutchinson
Jan 10, 2003·The Journal of Investigative Dermatology. Symposium Proceedings·Richard L EckertFrederic Bone
Aug 27, 2011·The Journal of Biological Chemistry·Alejandro A HidalgoDonald L Trump
Jan 27, 2012·Photochemistry and Photobiology·Joshua A DesotelleNihal Ahmad
Dec 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guoan ChenNithya Ramnath
Jul 2, 2010·Endocrinology·Josephia R MuindiCandace S Johnson
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Jan 16, 2013·Endocrine-related Cancer·Carlien LeyssensAnnemieke Verstuyf
Jan 27, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Belinda Byrne, JoEllen Welsh
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Apr 17, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Nithya RamnathSo Hee Kim
Feb 5, 2013·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Lindsey KennedyHeather Francis
Aug 30, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Lauren R HarmsJohn J McGrath
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Oct 7, 2004·Brain Research. Developmental Brain Research·Pauline KoDarryl Eyles
Jul 1, 2004·The Journal of Steroid Biochemistry and Molecular Biology·Donald L TrumpCandace S Johnson
Aug 3, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Belinda M Byrne, JoEllen Welsh
Aug 2, 2003·Journal of Pharmacological Sciences·Yoshiyuki MizushinaKengo Sakaguchi
Mar 23, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Candace S JohnsonDonald L Trump
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Mar 26, 2003·Cell Death and Differentiation·U FischerK Schulze-Osthoff
Sep 25, 2004·Journal of Cellular Biochemistry·Petra De HaesSiegfried Segaert

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