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

Marwa Kamel, Samia Shouman, Mahmoud El-Merzebany, Gokhan Kilic, Timothy Veenstra, Muhammad Saeed, Mohamed Wagih, Concepcion Diaz-Arrastia, Deepa Patel, Salama Salama

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 carcino-genesis 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 chromatog-raphy/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), Cyto-chrome 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 car-cinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.

Original languageEnglish (US)
Pages (from-to)310-321
Number of pages12
JournalJournal of Cancer
Volume3
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Metabolic Networks and Pathways
Estrogens
Tumor Necrosis Factor-alpha
Breast Neoplasms
DNA Adducts
Estrone
Estradiol
Catechol Estrogens
Catechols
Guaiacol
Adenine
Enzymes
Transferases
NADP
Reporter Genes
Cytochrome P-450 Enzyme System
Reverse Transcription
Real-Time Polymerase Chain Reaction
Mass Spectrometry
Oxidoreductases

Keywords

  • Breast cancer
  • DNA adducts
  • Estrogen metabo-lizing genes and enzymes
  • Estrogen metabolites
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Oncology

Cite this

Kamel, M., Shouman, S., El-Merzebany, M., Kilic, G., Veenstra, T., Saeed, M., ... Salama, S. (2012). Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells. Journal of Cancer, 3(1), 310-321. https://doi.org/10.7150/jca.4584

Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells. / Kamel, Marwa; Shouman, Samia; El-Merzebany, Mahmoud; Kilic, Gokhan; Veenstra, Timothy; Saeed, Muhammad; Wagih, Mohamed; Diaz-Arrastia, Concepcion; Patel, Deepa; Salama, Salama.

In: Journal of Cancer, Vol. 3, No. 1, 2012, p. 310-321.

Research output: Contribution to journalArticle

Kamel, M, Shouman, S, El-Merzebany, M, Kilic, G, Veenstra, T, Saeed, M, Wagih, M, Diaz-Arrastia, C, Patel, D & Salama, S 2012, 'Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells', Journal of Cancer, vol. 3, no. 1, pp. 310-321. https://doi.org/10.7150/jca.4584
Kamel, Marwa ; Shouman, Samia ; El-Merzebany, Mahmoud ; Kilic, Gokhan ; Veenstra, Timothy ; Saeed, Muhammad ; Wagih, Mohamed ; Diaz-Arrastia, Concepcion ; Patel, Deepa ; Salama, Salama. / Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells. In: Journal of Cancer. 2012 ; Vol. 3, No. 1. pp. 310-321.
@article{22baef368d754856aa04272fd3229b1d,
title = "Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells",
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 carcino-genesis 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 chromatog-raphy/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), Cyto-chrome 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 car-cinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.",
keywords = "Breast cancer, DNA adducts, Estrogen metabo-lizing genes and enzymes, Estrogen metabolites, Tumor necrosis factor-alpha",
author = "Marwa Kamel and Samia Shouman and Mahmoud El-Merzebany and Gokhan Kilic and Timothy Veenstra and Muhammad Saeed and Mohamed Wagih and Concepcion Diaz-Arrastia and Deepa Patel and Salama Salama",
year = "2012",
doi = "10.7150/jca.4584",
language = "English (US)",
volume = "3",
pages = "310--321",
journal = "Journal of Cancer",
issn = "1837-9664",
publisher = "Ivyspring International Publisher",
number = "1",

}

TY - JOUR

T1 - Effect of Tumour Necrosis Factor-Alpha on Estrogen Metabolic Pathways in Breast Cancer Cells

AU - Kamel, Marwa

AU - Shouman, Samia

AU - El-Merzebany, Mahmoud

AU - Kilic, Gokhan

AU - Veenstra, Timothy

AU - Saeed, Muhammad

AU - Wagih, Mohamed

AU - Diaz-Arrastia, Concepcion

AU - Patel, Deepa

AU - Salama, Salama

PY - 2012

Y1 - 2012

N2 - 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 carcino-genesis 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 chromatog-raphy/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), Cyto-chrome 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 car-cinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.

AB - 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 carcino-genesis 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 chromatog-raphy/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), Cyto-chrome 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 car-cinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.

KW - Breast cancer

KW - DNA adducts

KW - Estrogen metabo-lizing genes and enzymes

KW - Estrogen metabolites

KW - Tumor necrosis factor-alpha

UR - http://www.scopus.com/inward/record.url?scp=84875359965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875359965&partnerID=8YFLogxK

U2 - 10.7150/jca.4584

DO - 10.7150/jca.4584

M3 - Article

VL - 3

SP - 310

EP - 321

JO - Journal of Cancer

JF - Journal of Cancer

SN - 1837-9664

IS - 1

ER -