The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines

Eva Pozsgai, Andrew V Schally, Eniko Hocsak, Marta Zarandi, Ferenc Rick, Szabolcs Bellyei

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Growth hormone releasing hormone (GHRH) antagonists have been developed for the treatment of various cancers. We investigated the effects of a novel GHRH antagonist, MIA-602, on nine breast cancer cell lines, differing in their expression for estrogen-, progesterone- and HER-2 receptors. We detected the presence of pituitary-type GHRH receptors (pGHRH-R) on 6 of the 9 breast cancer cell lines. The main splice variant of pGHRH-R, SV1, was found on all 9 cell lines. MTT assay showed that following treatment with MIA-602, cell viability decreased significantly in all 9 cell lines. The reduction in cell viability was greater in cells positive for both pGHRH-R and SV1, than in cells positive for only SV1, but the difference was not significant. Using Western blotting, we demonstrated that the levels of phospho-Akt, -GSK3β and -ERK1/2 decreased significantly following exposure to MIA-602 and the level of phospho-p38 increased after treatment. The reduction of the phosphorylated anti-apoptotic proteins was significantly greater in cells where both pGHRH-R and SV1 were present, than where only SV1 was expressed. In conclusion, our study shows that MIA-602 is effective against a wide range of breast cancer cells in vitro, independently of their receptor positivity, suggesting the potential use of GHRH antagonists also in the treatment of triple-negative breast cancer. The effect of MIA-602 was mediated nearly as well in tumors that expressed only the SV1 receptor compared to those in which both SV1 and pGHRH-R were present, although a difference could be detected at the level of cell signaling.

Original languageEnglish
Pages (from-to)1025-1032
Number of pages8
JournalInternational Journal of Oncology
Volume39
Issue number4
DOIs
StatePublished - Oct 1 2011

Fingerprint

Growth Hormone-Releasing Hormone
Hormone Antagonists
Cell Proliferation
Breast Neoplasms
Cell Line
Pituitary Hormone-Regulating Hormone Receptors
Cell Survival
Triple Negative Breast Neoplasms
Apoptosis Regulatory Proteins
Growth Hormone
Progesterone
Neoplasms
Estrogens
Western Blotting
somatotropin releasing hormone receptor
GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-

Keywords

  • Akt
  • Breast cancer
  • ERK
  • Growth hormone releasing hormone antagonist
  • Growth hormone releasing hormone receptor
  • SV1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The effect of a novel antagonist of growth hormone releasing hormone on cell proliferation and on the key cell signaling pathways in nine different breast cancer cell lines. / Pozsgai, Eva; Schally, Andrew V; Hocsak, Eniko; Zarandi, Marta; Rick, Ferenc; Bellyei, Szabolcs.

In: International Journal of Oncology, Vol. 39, No. 4, 01.10.2011, p. 1025-1032.

Research output: Contribution to journalArticle

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