Overexpression of phosphorylated MARCKS in the nicotine-derived nitrosamine ketone induced lung cancer mice

  • Zhen Chen Department of Blood Transfusion, Beijing Military General Hospital, Beijing 100700
  • Ling-Yun Gu Department of Traditional Chinese Medicine, Beijing Military General Hospital, Beijing 100700
  • Jun Zhou Department of Blood Transfusion, Beijing Military General Hospital, Beijing 100700
  • Qin Wang Department of Blood Transfusion, Beijing Military General Hospital, Beijing 100700
  • Hui Gao Department of Traditional Chinese Medicine, Beijing Military General Hospital, Beijing 100 700
  • Zhong-He Yu Clinical Center of Oncology, Beijing Military General Hospital, Beijing 100700
Keywords: A/J mice, Lung cancer, NNK, Phosphorylated MARCKS

Abstract

Lung cancer is the most frequently occurring lethal cancers in men and women population. The aim of the present study is to observe the overexpression pattern of phosphorylated MARCKS in the nicotine-derived nitrosamine ketone (NNK) induced lung cancer mice. Pathogen-free female A/J mice were used for the present experiment to induce lung cancer by the carcinogen namely, NNK. At different time intervals namely, 5th, 6th and 7th month after NNK injection, lung tissue samples were collected. Immunohistochemistry in accordance with the immunoblotting techniques were used to confirm the overexpression of phosphorylated MARCKS in the NNK induced lung cancer mice model. The present study concludes that the phosphorylated MARCKS was overexpressed in the NNK induced lung cancer mice during the early stages of lung cancer and it may be used as a tool to detect the lung cancer in the initial stages. 

Downloads

Download data is not yet available.
Abstract
846
Download
296 Read
370

References

Bedard LL, Smith GB, Reid KR, Petsikas D, Massey TE. Investigation of the role of lipoxygenase in bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung. Chem Res Toxicol. 2002; 15: 1267-73.

Chen C-H, Statt S, Chiu C-L, Thai P, Arif M, Adler KB, Wu R. Targeting myristoylated alanine-rich C Kinase substrate phosphorylation site domain in lung cancer: Mechanisms and therapeutic implications. Am J Respir Crit Care Med. 2014; 190: 1127-38.

Chen X, Rotenberg SA. PhosphoMARCKS drives motility of mouse melanoma cells. Cell Signal. 2010; 22: 1097-103.

Cogliano V, Straif K, Baan R, Grosse Y, Secretan B, Ghissassi FE. Smokeless tobacco and tobacco-related nitrosamines. Lancet Oncol. 2004; 5: 708.

Dedhia HV, Parker JE. A new era for lung cancer detection. Comm Oncol. 2011; 8: 442-44.

Eckert RE, Neuder LE, Park J, Adler KB, Jones SL. Myristoylated alanine-rich C-kinase substrate (MARCKS) protein regulation of human neutrophil migration. Am J Respir Cell Mol Biol. 2010; 42: 586-94.

Erusalimsky J, Brooks S, Herget T, Morris C, Rozengurt E. Molecular cloning and characterization of the acidic 80-kDa protein kinase C substrate from rat brain: Identification as a glycoprotein. J Biol Chem. 1991; 266: 7073-80.

Gambhir A, Hangyás-Mihályné G, Zaitseva I, Cafiso DS, Wang J, Murray D, Pentyala SN, Smith SO, McLaughlin S. Electrostatic sequestration of PIP2 on phospholipid membranes by basic/aromatic regions of proteins. Biophy J. 2004; 86: 2188-207.

Ghoul A, Serova M, Benhadji K, Cvitkovic E, Faivre S, Philips E, Calvo F, Lokiec F, Raymond E. Protein kinase C ? and ? are members of a large kinase family of high potential for novel anticancer targeted therapy. Targeted Oncol. 2006; 1: 42-53.

Green TD, Crews AL, Park J, Fang S, Adler KB. Regulation of mucin secretion and inflammation in asthma: A role for MARCKS protein? Biochimica et Biophysica Acta (BBA)-General Subjects. 2011; 1810: 1110-13.

Harlan DM, Graff J, Stumpo D, Eddy R, Shows T, Boyle JM, Blackshear P. The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization. J Biol Chem. 1991; 266: 14399-405.

Li Y, Martin LD, Spizz G, Adler KB. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J Biol Chem. 2001; 276: 40982-90.

McLaughlin S, Murray D. Plasma membrane phosphoinositide organization by protein electrostatics. Nature 2005; 438: 605-11.

Park J-A, Crews AL, Lampe WR, Fang S, Park J, Adler KB. Protein kinase C? regulates airway mucin secretion via phosphorylation of MARCKS protein. Am J Pathol. 2007; 171: 1822-30.

Reddy M, Fernandes M, Salgia R, Levine R, Griffin J, Sattler M. NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases. Leukemia 2010; 25: 281-89.

Seykora JT, Ravetch JV, Aderem A. Cloning and molecular characterization of the murine macrophage" 68-kDa" protein kinase C substrate and its regulation by bacterial lipopolysaccharide. Proc Natl Acad Sci USA. 1991; 88: 2505-09.

Singer M, Martin LD, Vargaftig BB, Park J, Gruber AD, Li Y, Adler KB. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nature Med. 2004; 10: 193-96.

Song P, Sekhon H, Proskocil B, Blusztajn J, Mark G, Spindel E. Synthesis of acetylcholine by lung cancer. Life Sci. 2003; 72: 2159-68.

Stumpo DJ, Graff JM, Albert KA, Greengard P, Blackshear PJ. Molecular cloning, characterization, and expression of a cDNA encoding the" 80-to 87-kDa" myristoylated alanine-rich C kinase substrate: A major cellular substrate for protein kinase C. Proc Natl Acad Sci USA. 1989; 86: 4012-16.

Techasen A, Loilome W, Namwat N, Takahashi E, Sugihara E, Puapairoj A, Miwa M, Saya H, Yongvanit P. Myristoylated alanine?rich C kinase substrate phosphorylation promotes cholangiocarcinoma cell migration and metastasis via the protein kinase C?dependent pathway. Cancer Sci. 2010; 101: 658-65.

Wang H, Tan W, Hao B, Miao X, Zhou G, He F, Lin D. Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Res. 2003; 63: 8057-61.

Published
2015-01-29
How to Cite
Chen, Z., L.-Y. Gu, J. Zhou, Q. Wang, H. Gao, and Z.-H. Yu. “Overexpression of Phosphorylated MARCKS in the Nicotine-Derived Nitrosamine Ketone Induced Lung Cancer Mice”. Bangladesh Journal of Pharmacology, Vol. 10, no. 1, Jan. 2015, pp. 92-96, doi:10.3329/bjp.v10i1.21185.
Section
Research Articles