Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

E. M. Nilsson (Corresponding Author), L. J. S. Brokken, Elli Narvi, Marko Kallio, P. L. Härkönen

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)

Abstract

Fibroblast growth factor-8 (FGF-8) is implicated in the development and progression of breast cancer and its levels are frequently elevated in breast tumors. The mechanisms driving FGF-8-mediated tumorigenesis are not well understood. Herein we aimed to identify target genes associated with FGF-8b-mediated breast cancer cell proliferation by carrying out a cDNA microarray analysis of genes expressed in estrogen receptor negative S115 breast cancer cells treated with FGF-8b for various time periods in comparison with those expressed in non-treated cells. Gene and protein expression was validated for selected genes by qPCR and western blotting respectively. Furthermore, using TRANSBIG data, the expression of human orthologs of FGF-8-regulated genes was correlated to the Nottingham prognostic index and estrogen receptor status. The analysis revealed a number of significantly up- and down-regulated genes in response to FGF-8b at all treatment times. The most differentially expressed genes were genes related to cell cycle regulation, mitosis, cancer, and cell death. Several key regulators of early cell cycle progression such as Btg2 and cyclin D1, as well as regulators of mitosis, including cyclin B, Plk1, survivin, and aurora kinase A, were identified as novel targets for FGF-8b, some of which were additionally shown to correlate with prognosis and ER status in human breast cancer. The results suggest that in stimulation of proliferation FGF-8b not only promotes cell cycle progression through the G1 restriction point but also regulates key proteins involved in chromosomal segregation during mitosis and cytokinesis of breast cancer cells.
Original languageEnglish
Pages (from-to)104-115
JournalMolecular and Cellular Endocrinology
Volume358
Issue number1
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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Fibroblast Growth Factor 8
Cell Cycle
Genes
Cells
Breast Neoplasms
Mitosis
Estrogen Receptors
Aurora Kinase A
Cyclin B
G1 Phase Cell Cycle Checkpoints
Cytokinesis
Cyclin D1
Cell proliferation
Cell death
Microarray Analysis
Microarrays
Oligonucleotide Array Sequence Analysis
Tumors
Carcinogenesis
Proteins

Keywords

  • cDNA microarray
  • Breast tumorigenesis
  • Mitosis
  • Cyclins
  • Ingenuity signaling pathway
  • Nottingham prognostic index

Cite this

Nilsson, E. M. ; Brokken, L. J. S. ; Narvi, Elli ; Kallio, Marko ; Härkönen, P. L. / Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells. In: Molecular and Cellular Endocrinology. 2012 ; Vol. 358, No. 1. pp. 104-115.
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Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells. / Nilsson, E. M. (Corresponding Author); Brokken, L. J. S.; Narvi, Elli; Kallio, Marko; Härkönen, P. L.

In: Molecular and Cellular Endocrinology, Vol. 358, No. 1, 2012, p. 104-115.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells

AU - Nilsson, E. M.

AU - Brokken, L. J. S.

AU - Narvi, Elli

AU - Kallio, Marko

AU - Härkönen, P. L.

PY - 2012

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N2 - Fibroblast growth factor-8 (FGF-8) is implicated in the development and progression of breast cancer and its levels are frequently elevated in breast tumors. The mechanisms driving FGF-8-mediated tumorigenesis are not well understood. Herein we aimed to identify target genes associated with FGF-8b-mediated breast cancer cell proliferation by carrying out a cDNA microarray analysis of genes expressed in estrogen receptor negative S115 breast cancer cells treated with FGF-8b for various time periods in comparison with those expressed in non-treated cells. Gene and protein expression was validated for selected genes by qPCR and western blotting respectively. Furthermore, using TRANSBIG data, the expression of human orthologs of FGF-8-regulated genes was correlated to the Nottingham prognostic index and estrogen receptor status. The analysis revealed a number of significantly up- and down-regulated genes in response to FGF-8b at all treatment times. The most differentially expressed genes were genes related to cell cycle regulation, mitosis, cancer, and cell death. Several key regulators of early cell cycle progression such as Btg2 and cyclin D1, as well as regulators of mitosis, including cyclin B, Plk1, survivin, and aurora kinase A, were identified as novel targets for FGF-8b, some of which were additionally shown to correlate with prognosis and ER status in human breast cancer. The results suggest that in stimulation of proliferation FGF-8b not only promotes cell cycle progression through the G1 restriction point but also regulates key proteins involved in chromosomal segregation during mitosis and cytokinesis of breast cancer cells.

AB - Fibroblast growth factor-8 (FGF-8) is implicated in the development and progression of breast cancer and its levels are frequently elevated in breast tumors. The mechanisms driving FGF-8-mediated tumorigenesis are not well understood. Herein we aimed to identify target genes associated with FGF-8b-mediated breast cancer cell proliferation by carrying out a cDNA microarray analysis of genes expressed in estrogen receptor negative S115 breast cancer cells treated with FGF-8b for various time periods in comparison with those expressed in non-treated cells. Gene and protein expression was validated for selected genes by qPCR and western blotting respectively. Furthermore, using TRANSBIG data, the expression of human orthologs of FGF-8-regulated genes was correlated to the Nottingham prognostic index and estrogen receptor status. The analysis revealed a number of significantly up- and down-regulated genes in response to FGF-8b at all treatment times. The most differentially expressed genes were genes related to cell cycle regulation, mitosis, cancer, and cell death. Several key regulators of early cell cycle progression such as Btg2 and cyclin D1, as well as regulators of mitosis, including cyclin B, Plk1, survivin, and aurora kinase A, were identified as novel targets for FGF-8b, some of which were additionally shown to correlate with prognosis and ER status in human breast cancer. The results suggest that in stimulation of proliferation FGF-8b not only promotes cell cycle progression through the G1 restriction point but also regulates key proteins involved in chromosomal segregation during mitosis and cytokinesis of breast cancer cells.

KW - cDNA microarray

KW - Breast tumorigenesis

KW - Mitosis

KW - Cyclins

KW - Ingenuity signaling pathway

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DO - 10.1016/j.mce.2012.03.009

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JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

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ER -