SGK1, a potential regulator of c-fms related breast cancer aggressiveness

Jacob Tangir, Nathalie Bonafé, Maureen Gilmore-Hebert, Octavian Henegariu, Setsuko K Chambers

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The aggressive behavior of breast cancer cells can at times be modulated by hormonal mechanisms. Exposure to glucocorticoids (GC) has been shown to stimulate the invasiveness, motility and adhesiveness of breast cancer cells containing the glucocorticoid receptor. This is largely explained by GC-associated overexpression of the c-fms proto-oncogene, which encodes the receptor for the colony stimulating factor-1 (CSF-1). Our objective is to investigate additional GC-associated genetic alterations that could modulate c-fms related malignant behavior in breast cancer cells. A microarray technique using an oligonucleotide array representing 16,700 known expressed human genes was used to analyze the gene expression profile of breast cancer cells exposed to dexamethasone (Dex) or vehicle. Results were confirmed by western blot analysis. Six genes were found to be consistently differentially overexpressed in the Dex-exposed cells compared to control. We focused on serum-glucose kinase 1 (SGK1), a serine-threonine kinase known to be involved in intracellular signal transduction pathways and induced by GC and serum. An adhesion assay was performed on extracellular matrix after exposing the breast cancer cells to Dex, CSF-1 or to Dex or CSF-1 plus LY294002, a functional inhibitor of SGK1 action. Exposure to LY294002 significantly decreased both CSF-1 and Dex-induced adhesiveness to the level of control cells. SGK1 may act as a downstream intracellular regulator of c-fms, particularly of c-fms-induced adhesiveness of breast cancer cells after exposure to GC or CSF-I. This finding may have implications for potential therapeutic interventions aimed at decreasing the aggressiveness of breast cancer cells.

Original languageEnglish (US)
Pages (from-to)477-483
Number of pages7
JournalClinical and Experimental Metastasis
Volume21
Issue number6
DOIs
StatePublished - Oct 2004

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Phosphotransferases
Breast Neoplasms
Glucose
Macrophage Colony-Stimulating Factor
Dexamethasone
Glucocorticoids
Serum
Adhesiveness
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
fms Genes
Protein-Serine-Threonine Kinases
Glucocorticoid Receptors
Oligonucleotide Array Sequence Analysis
Transcriptome
Genes
Extracellular Matrix
Signal Transduction
Western Blotting

Keywords

  • Breast cancer
  • c-fms
  • CSF-1
  • Glucocorticoids SGK1

ASJC Scopus subject areas

  • Cancer Research

Cite this

SGK1, a potential regulator of c-fms related breast cancer aggressiveness. / Tangir, Jacob; Bonafé, Nathalie; Gilmore-Hebert, Maureen; Henegariu, Octavian; Chambers, Setsuko K.

In: Clinical and Experimental Metastasis, Vol. 21, No. 6, 10.2004, p. 477-483.

Research output: Contribution to journalArticle

Tangir, Jacob ; Bonafé, Nathalie ; Gilmore-Hebert, Maureen ; Henegariu, Octavian ; Chambers, Setsuko K. / SGK1, a potential regulator of c-fms related breast cancer aggressiveness. In: Clinical and Experimental Metastasis. 2004 ; Vol. 21, No. 6. pp. 477-483.
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