Estrogen-receptor status determines differential regulation of α1- and α2-adrenoceptor-mediated cell survival, angiogenesis, and intracellular signaling responses in breast cancer cell lines

Hannah P. Priyanka, Uday P. Pratap, Rahul S. Nair, Ramasamy Vasantharekha, Srinivasan ThyagaRajan

Research output: Contribution to journalArticlepeer-review

Abstract

Psychosocial stress promotes cancer pathogenesis involving angiogenesis through alterations in neuroendocrine-immune functions that may involve adrenoceptor (AR)-dependent signaling mechanisms in the brain, lymphoid organs, and cancerous cells. Various concentrations of α1- and α2- AR-specific agonists and antagonists were incubated in vitro with estrogen receptor-positive (ER +) MCF-7, and ER (-) MDA MB-231 cells to examine the secretions of VEGF-A, VEGF-C, and nitric oxide (NO), and expression of signaling molecules- p-ERK, p-CREB, and p-Akt on the proliferation of breast cancer cell lines. Cellular proliferation, VEGF-A and NO secretion, expression of p-ERK, p-CREB, and p-Akt were enhanced in MCF-7 cells treated with α1-AR agonist while VEGF-C secretion alone was enhanced in MDA MB-231 cells. Treatment of MCF-7 and MDA MB-231 cells with α2- AR agonist similarly enhanced proliferation and decreased NO production and p-CREB expression while VEGF-C secretion was decreased in MCF-7 cells and p-Akt expression was decreased in MDA MB-231 cells. α1-AR inhibition reversed cellular proliferation and VEGF-A secretion by MCF-7 cells while α2-AR inhibition reversed the proliferation of MCF-7 and MDA MB-231 cells and VEGF-C secretion by MCF-7 cells. Taken together, breast cancer pathogenesis may be influenced by distinct α-AR-mediated signaling mechanisms on angiogenesis and lymphangiogenesis that are dependent on estrogen receptor status.

Original languageEnglish (US)
Article number92
JournalMedical Oncology
Volume41
Issue number5
DOIs
StatePublished - May 2024

Keywords

  • Clonidine
  • Idazoxan
  • Phenylephrine
  • Prazosin
  • Signaling molecules

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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