Advanced

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

Nilsson, E M; Brokken, Leon LU ; Narvi, E; Kallio, M J and Härkönen, Pirkko LU (2012) In Molecular and Cellular Endocrinology 358(1). p.104-115
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Endocrinology
volume
358
issue
1
pages
104 - 115
publisher
Elsevier
external identifiers
  • wos:000304638800013
  • pmid:22465097
  • scopus:84860424403
ISSN
1872-8057
DOI
10.1016/j.mce.2012.03.009
language
English
LU publication?
yes
id
3cca6b4f-4c93-48af-a1bc-9b7a6136c0ed (old id 2520026)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22465097?dopt=Abstract
date added to LUP
2012-05-04 13:21:36
date last changed
2017-01-01 04:05:33
@article{3cca6b4f-4c93-48af-a1bc-9b7a6136c0ed,
  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.},
  author       = {Nilsson, E M and Brokken, Leon and Narvi, E and Kallio, M J and Härkönen, Pirkko},
  issn         = {1872-8057},
  language     = {eng},
  number       = {1},
  pages        = {104--115},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells.},
  url          = {http://dx.doi.org/10.1016/j.mce.2012.03.009},
  volume       = {358},
  year         = {2012},
}