Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells

Keya De Mukhopadhyay, Zhao Liu, Abhik Bandyopadhyay, Nameer B Kirma, Rajeshwar R Tekmal, Shui Wang, Luzhe Sun

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα) positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

Original languageEnglish (US)
Article numbere0121136
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 2 2015

Fingerprint

Aromatase
Estrogen Receptor alpha
Estrogen Receptors
breast neoplasms
Cells
Breast Neoplasms
Survival
Estrogens
estrogens
Neoplasms
Aromatase Inhibitors
Testosterone
Suspensions
testosterone
Anoikis
Blood Circulation
Lymph
Stromal Cells
Growth
lymph

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells. / De Mukhopadhyay, Keya; Liu, Zhao; Bandyopadhyay, Abhik; Kirma, Nameer B; Tekmal, Rajeshwar R; Wang, Shui; Sun, Luzhe.

In: PLoS One, Vol. 10, No. 4, e0121136, 02.04.2015.

Research output: Contribution to journalArticle

De Mukhopadhyay, Keya ; Liu, Zhao ; Bandyopadhyay, Abhik ; Kirma, Nameer B ; Tekmal, Rajeshwar R ; Wang, Shui ; Sun, Luzhe. / Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells. In: PLoS One. 2015 ; Vol. 10, No. 4.
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