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.: Home > Journal of Cancer > 2012 > Volume 3 Number 40 > Department of Obstetrics and Gynecology, Baylor College of Medicine, One Baylor Plaza MS: BCM 610, Houston, TX 77030, United States.

Effect of Tumour Necrosis Factor - Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells

Department of Obstetrics and Gynecology, Baylor College of Medicine, One Baylor Plaza MS: BCM 610, Houston, TX 77030, United States.
el.: +1 832 824 4188; fax: +1 832 825 4190. E-mail addresses:salama@bcm. edu,salamas@hotmail.com
Abstract :

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. Estrogen metabolic pathway is also involved in breast carcinogenesis and DNA adducts formation. In this study we investigated the effect of TNF-α on the estrogen metabolic pathway in MCF-7, a breast cancer cell line. Capillary liquid chromatography/mass spectrometry (LC/MS) and High performance liquid chromatography (HPLC) were used for analysis of estrogen metabolites and estrogen-DNA adducts levels respectively. Reporter gene assay, Real time reverse transcription polymerase chain reaction (real time RT-PCR) and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes. TNF-α significantly increased the total EM and decreased the estrone (E1) / 17-β estradiol (E2) ratio. Moreover, it altered the expression of genes and enzymes involved in E2 activation and deactivation pathways e.g. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), Catechol-O-methyl transferase (COMT) and Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2-hydroxyestradiol (2-OHE2) with decreased levels of methylated catechols e.g. 2-methoxy estradiol (2-MeOE2). DNA adducts especially 4-OHE1-[2]-1-N3 Adenine was significantly increased. TNF-α directs the estrogen metabolism into more hormonally active and carcinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.

Keywords :
Breast cancer; Tumor necrosis factor - alpha; Estrogen metabolites; Estrogen metab o- lizing genes and enzymes; DNA adducts

Date Deposited : 05 Jan 2015 14:28

Last Modified : 16 Jan 2015 10:56

Official URL: http://www.jcancer.org/

Volume 3, Number 40, - 2012

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