Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells.
(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:
https://lup.lub.lu.se/record/2520026
- author
- Nilsson, E M ; Brokken, Leon LU ; Narvi, E ; Kallio, M J and Härkönen, Pirkko LU
- organization
- publishing date
- 2012
- 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
- pmid:22465097
- ISSN
- 1872-8057
- DOI
- 10.1016/j.mce.2012.03.009
- language
- English
- LU publication?
- yes
- additional info
- Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:26.
- 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
- 2016-04-01 11:00:59
- date last changed
- 2022-03-27 21:43:58
@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 = {{https://lup.lub.lu.se/search/files/2307051/2541072.pdf}}, doi = {{10.1016/j.mce.2012.03.009}}, volume = {{358}}, year = {{2012}}, }