Growth hormone receptor promotes breast cancer progression via the BRAF/MEK/ERK signaling pathway

FEBS Open Bio. 2020 Jun;10(6):1013-1020. doi: 10.1002/2211-5463.12816. Epub 2020 May 6.

Abstract

Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably inhibited GHR in breast cancer cell lines, which were observed to reduce cell proliferation, tumor growth and induction of apoptosis, and arrest the cell-cycle arrest at the G1-S phase transition. In addition, GHR silencing suppressed the protein levels of B-Raf proto-oncogene, serine/threonine kinase (BRAF), Mitogen-activated protein kinase kinase (MEK) and Extracellular regulated protein kinases (ERK). These findings suggest that GHR may mediate breast cell progression and apoptosis through control of the cell cycle via the BRAF/MEK/ERK signaling pathway.

Keywords: BRAF/MEK/ERK signaling pathway; GHR; apoptosis; breast cancer; cell cycle.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Apoptosis
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Humans
  • MAP Kinase Signaling System
  • Mastectomy
  • Mice
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins B-raf / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • somatotropin-binding protein