Progestin stimulation of manganese superoxide dismutase and invasive properties in T47D human breast cancer cells

Aaron K Holley; Kelley K Kiningham; Douglas R Spitz; Dean P Edwards; Jeffrey T Jenkins; Michael R Moore

doi:10.1016/j.jsbmb.2009.06.004

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Progestin stimulation of manganese superoxide dismutase and invasive properties in T47D human breast cancer cells

Journal article

Peer reviewed

Progestin stimulation of manganese superoxide dismutase and invasive properties in T47D human breast cancer cells

Aaron K Holley, Kelley K Kiningham, Douglas R Spitz, Dean P Edwards, Jeffrey T Jenkins and Michael R Moore

The Journal of steroid biochemistry and molecular biology, Vol.117(1), pp.23-30

2009

DOI: 10.1016/j.jsbmb.2009.06.004

PMCID: PMC2749892

PMID: 19563893

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Abstract

Superoxide dismutase (SOD) occurs in two intracellular forms in mammals, copper–zinc SOD (CuZnSOD), found in the cytoplasm, mitochondria and nucleus, and manganese superoxide dismutase (MnSOD), in mitochondria. Changes in MnSOD expression (as compared to normal cells) have been reported in several forms of cancer, and these changes have been associated with regulation of cell proliferation, cell death, and metastasis. We have found that progestins stimulate MnSOD in T47D human breast cancer cells in a time and physiological concentration-dependent manner, exhibiting specificity for progestins and inhibition by the antiprogestin RU486. Progestin stimulation occurs at the level of mRNA, protein, and enzyme activity. Cycloheximide inhibits stimulation at the mRNA level, suggesting that progestin induction of MnSOD mRNA depends on synthesis of protein. Experiments with the MEK inhibitor UO126 suggest involvement of the MAP kinase signal transduction pathway. Finally, MnSOD-directed siRNA lowers progestin-stimulated MnSOD and inhibits progestin stimulation of migration and invasion, suggesting that up-regulation of MnSOD may be involved in the mechanism of progestin stimulation of invasive properties. To our knowledge, this is the first characterization of progestin stimulation of MnSOD in human breast cancer cells.

Breast Cancer

Progesterone

T47D cells

Manganese superoxide dismutase

Details

Title: Subtitle: Progestin stimulation of manganese superoxide dismutase and invasive properties in T47D human breast cancer cells
Creators: Aaron K Holley - Department of Biochemistry & Microbiology, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive BBSC, Huntington, WV 25755-9320, USA
Kelley K Kiningham - Pharmaceutical Sciences, Belmont University School of Pharmacy, Nashville, TN, USA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Dean P Edwards - Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
Jeffrey T Jenkins - Department of Biochemistry & Microbiology, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive BBSC, Huntington, WV 25755-9320, USA
Michael R Moore - Department of Biochemistry & Microbiology, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive BBSC, Huntington, WV 25755-9320, USA
Resource Type: Journal article
Publication Details: The Journal of steroid biochemistry and molecular biology, Vol.117(1), pp.23-30
DOI: 10.1016/j.jsbmb.2009.06.004
PMID: 19563893
PMCID: PMC2749892
NLM abbreviation: J Steroid Biochem Mol Biol
ISSN: 0960-0760
eISSN: 1879-1220
Publisher: Elsevier BV
Language: English
Date published: 2009
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047757502771

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