2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells

Marisol Quezada, Jorge Diaz, Soledad Henriquez, Maria Loreto Bravo, Evelyn Aranda, Barbara Oliva, Manuel Villalon, Sumie Kato, Mauricio A. Cuello, Jan J. Brosens, Carol A. Lange, Gareth I. Owen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

2-Methoxyestradiol (2ME) is an endogenous metabolite of 17β-estradiol with antiangiogenic and antitumor properties, although its mechanisms of action remain unclear. Progestins in hormone replacement therapy increase the risk of breast cancer. Progesterone also enhances the procoagulant activity and invasive potential of progesterone receptor (PR)-positive breast cancer cell lines, an effect largely mediated by induction of tissue factor (TF), the cellular activator of the coagulation cascade. Here we show that 2ME abrogates the induction TF expression in progesterone-treated breast cancer cells via a mechanism that does not involve the estrogen receptor. Instead, we demonstrate that by selectively antagonizing ERK1/2 signaling in breast cancer cells, 2ME limits the transactivation potential of ligand-bound PR and inhibits the expression of endogenous progesterone targets, such as TF and signal transducer and activator of transcription 5. We further demonstrate that 2ME can alter the phosphorylation status of PR. Thus, 2ME prevents progesterone-dependent increase in breast cancer cell invasiveness and procoagulant activity by uncoupling PR from the ERK1/2 signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalHormones and Cancer
Volume1
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Thromboplastin
Progesterone
Progesterone Receptors
Breast Neoplasms
STAT5 Transcription Factor
Hormone Replacement Therapy
Progestins
Estrogen Receptors
Transcriptional Activation
Estradiol
Signal Transduction
Phosphorylation
2-methoxyestradiol
Ligands
Cell Line

Keywords

  • 2-Methoxyestradiol
  • Breast cancer
  • Progesterone receptor
  • STAT5
  • Tissue factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems

Cite this

Quezada, M., Diaz, J., Henriquez, S., Bravo, M. L., Aranda, E., Oliva, B., ... Owen, G. I. (2010). 2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells. Hormones and Cancer, 1(3), 117-126. https://doi.org/10.1007/s12672-010-0019-5

2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells. / Quezada, Marisol; Diaz, Jorge; Henriquez, Soledad; Bravo, Maria Loreto; Aranda, Evelyn; Oliva, Barbara; Villalon, Manuel; Kato, Sumie; Cuello, Mauricio A.; Brosens, Jan J.; Lange, Carol A.; Owen, Gareth I.

In: Hormones and Cancer, Vol. 1, No. 3, 2010, p. 117-126.

Research output: Contribution to journalArticle

Quezada, M, Diaz, J, Henriquez, S, Bravo, ML, Aranda, E, Oliva, B, Villalon, M, Kato, S, Cuello, MA, Brosens, JJ, Lange, CA & Owen, GI 2010, '2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells', Hormones and Cancer, vol. 1, no. 3, pp. 117-126. https://doi.org/10.1007/s12672-010-0019-5
Quezada, Marisol ; Diaz, Jorge ; Henriquez, Soledad ; Bravo, Maria Loreto ; Aranda, Evelyn ; Oliva, Barbara ; Villalon, Manuel ; Kato, Sumie ; Cuello, Mauricio A. ; Brosens, Jan J. ; Lange, Carol A. ; Owen, Gareth I. / 2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells. In: Hormones and Cancer. 2010 ; Vol. 1, No. 3. pp. 117-126.
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