Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway

John A III Copland, Yow Jiun Jeng, Zuzana Strakova, Kirk L. Ives, Mark R. Hellmich, Melvyn S. Soloff

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Oxytocin (OT) receptors (OTRs) have been demonstrated in a number of human breast tumors and tumor cells, but it was not clear whether the receptors were functional. We examined the regulation and function of OTR in a tumor cell line, Hs578T, derived from human breast. These cells expressed moderate levels of OTR when cultured in 10% FBS, as demonstrated by RT-PCR and binding analyses. Serum deprivation resulted in the loss of OTRs, with no effect on cell viability. Restoration of serum and addition of 1 μM dexamethasone (DEX) increased OTR levels by about 9-fold. Up-regulation was blocked by the addition of phospholipase C and PKC inhibitors. Serum/DEX treatment also increased steady state OTR messenger RNA levels. OT increased intracellular Ca2+ in a time- and dose-responsive manner, and the effects of OT were lost when OTRs were down-regulated by serum starvation. Serum/DEX up-regulation of OTR restored the responsiveness to OT. OT also stimulated ERK-2 (extracellular signal-regulated protein kinase) phosphorylation and PGE2 synthesis in Hs578T cells. In addition to showing that OTRs in the breast tumor cells are functional, these studies show that Hs578T cells can be used to study molecular regulation of OTR gene expression and intracellular signaling pathways stimulated by OT.

Original languageEnglish (US)
Pages (from-to)2258-2267
Number of pages10
JournalEndocrinology
Volume140
Issue number5
StatePublished - 1999
Externally publishedYes

Fingerprint

Oxytocin
Protein Kinase C
Breast
Up-Regulation
Dexamethasone
Serum
Breast Neoplasms
Oxytocin Receptors
Extracellular Signal-Regulated MAP Kinases
Type C Phospholipases
Starvation
Tumor Cell Line
Dinoprostone
Protein Kinases
Cell Survival
Phosphorylation
human OXTR protein
Gene Expression
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. / Copland, John A III; Jeng, Yow Jiun; Strakova, Zuzana; Ives, Kirk L.; Hellmich, Mark R.; Soloff, Melvyn S.

In: Endocrinology, Vol. 140, No. 5, 1999, p. 2258-2267.

Research output: Contribution to journalArticle

Copland, John A III ; Jeng, Yow Jiun ; Strakova, Zuzana ; Ives, Kirk L. ; Hellmich, Mark R. ; Soloff, Melvyn S. / Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. In: Endocrinology. 1999 ; Vol. 140, No. 5. pp. 2258-2267.
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