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IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells

Perks, C. M. ; Vernon, E. G. ; Rosendahl, Ann LU ; Tonge, D. and Holly, J. M. P. (2007) In Oncogene 26(40). p.5966-5972
Abstract
The dual-function phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) is the second most frequently mutated gene in human cancers. PTEN counteracts the functions of many growth factors, the most prevalent of which is insulin-like growth factor II ( IGF-II). PTEN expression is stimulated by IGF-II forming a feedback loop. Investigating IGF-binding protein ( IGFBP) modulation of IGF-II actions on MCF-7 breast cancer cells, we found that IGFBP-2 also regulates PTEN. The MCF-7 cells were not responsive to high doses of IGF-II due to induction of PTEN, which was not observed with an IGF-II-analog that does not bind to IGFBPs or in the presence of an inhibitor that prevents IGFs associating with IGFBPs. These cells predominantly... (More)
The dual-function phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) is the second most frequently mutated gene in human cancers. PTEN counteracts the functions of many growth factors, the most prevalent of which is insulin-like growth factor II ( IGF-II). PTEN expression is stimulated by IGF-II forming a feedback loop. Investigating IGF-binding protein ( IGFBP) modulation of IGF-II actions on MCF-7 breast cancer cells, we found that IGFBP-2 also regulates PTEN. The MCF-7 cells were not responsive to high doses of IGF-II due to induction of PTEN, which was not observed with an IGF-II-analog that does not bind to IGFBPs or in the presence of an inhibitor that prevents IGFs associating with IGFBPs. These cells predominantly produce IGFBP-2: blocking IGFBP-2 with a specific antibody, or preventing IGFBP-2 binding to integrins, restored the induction of PTEN and the cells were non-responsive to high doses of the IGF-II-analog. Our. findings indicate that breast cancer cells do not respond to high doses of IGF-II due to induction of PTEN, but IGFBP-2, when free from IGF-II can suppress PTEN. Levels of IGFBP-2 are elevated frequently in human tumors: its ability to regulate PTEN could have important implications in relation to therapeutic strategies targeting growth factor pathways. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IGF-II, IGFBP-2, PTEN
in
Oncogene
volume
26
issue
40
pages
5966 - 5972
publisher
Nature Publishing Group
external identifiers
  • wos:000249123100014
  • scopus:35148818315
ISSN
1476-5594
DOI
10.1038/sj.onc.1210397
language
English
LU publication?
yes
id
8ed5b4c1-6b06-4760-9753-2599788f071f (old id 687662)
date added to LUP
2016-04-01 12:32:06
date last changed
2022-01-27 06:22:02
@article{8ed5b4c1-6b06-4760-9753-2599788f071f,
  abstract     = {{The dual-function phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) is the second most frequently mutated gene in human cancers. PTEN counteracts the functions of many growth factors, the most prevalent of which is insulin-like growth factor II ( IGF-II). PTEN expression is stimulated by IGF-II forming a feedback loop. Investigating IGF-binding protein ( IGFBP) modulation of IGF-II actions on MCF-7 breast cancer cells, we found that IGFBP-2 also regulates PTEN. The MCF-7 cells were not responsive to high doses of IGF-II due to induction of PTEN, which was not observed with an IGF-II-analog that does not bind to IGFBPs or in the presence of an inhibitor that prevents IGFs associating with IGFBPs. These cells predominantly produce IGFBP-2: blocking IGFBP-2 with a specific antibody, or preventing IGFBP-2 binding to integrins, restored the induction of PTEN and the cells were non-responsive to high doses of the IGF-II-analog. Our. findings indicate that breast cancer cells do not respond to high doses of IGF-II due to induction of PTEN, but IGFBP-2, when free from IGF-II can suppress PTEN. Levels of IGFBP-2 are elevated frequently in human tumors: its ability to regulate PTEN could have important implications in relation to therapeutic strategies targeting growth factor pathways.}},
  author       = {{Perks, C. M. and Vernon, E. G. and Rosendahl, Ann and Tonge, D. and Holly, J. M. P.}},
  issn         = {{1476-5594}},
  keywords     = {{IGF-II; IGFBP-2; PTEN}},
  language     = {{eng}},
  number       = {{40}},
  pages        = {{5966--5972}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Oncogene}},
  title        = {{IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells}},
  url          = {{http://dx.doi.org/10.1038/sj.onc.1210397}},
  doi          = {{10.1038/sj.onc.1210397}},
  volume       = {{26}},
  year         = {{2007}},
}