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The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node

Loden, M; Stighall, Maria LU ; Nielsen, HN; Roos, G; Emdin, SO; Ostlund, H and Landberg, Göran LU (2002) In Oncogene 21(30). p.4680-4690
Abstract
In an attempt to identify subtypes of breast cancer and pinpoint patterns of cell cycle regulatory defects associated with clinical behaviour, proliferation and other transformation associated events, a multitude of cell cycle regulatory proteins were analysed in a material of 113 primary breast cancers. Increased proliferation was observed in two different scenarios; (1) with high cyclin D1 and elevated retinoblastoma protein (pRb) phosphorylation, (cyclin D1(high) tumours) or (2) with high cyclin E protein but low cyclin D1 and lack of corresponding pRb phosphorylation (cyclin E high tumours) indicative of an interrupted pRb pathway. Characteristic for cyclin E-high tumours were further defects in p53, p27 and bcl-2, while c-erbB2... (More)
In an attempt to identify subtypes of breast cancer and pinpoint patterns of cell cycle regulatory defects associated with clinical behaviour, proliferation and other transformation associated events, a multitude of cell cycle regulatory proteins were analysed in a material of 113 primary breast cancers. Increased proliferation was observed in two different scenarios; (1) with high cyclin D1 and elevated retinoblastoma protein (pRb) phosphorylation, (cyclin D1(high) tumours) or (2) with high cyclin E protein but low cyclin D1 and lack of corresponding pRb phosphorylation (cyclin E high tumours) indicative of an interrupted pRb pathway. Characteristic for cyclin E-high tumours were further defects in p53, p27 and bcl-2, while c-erbB2 overexpression and c-myc amplification was found in both cyclin D1(high) and E-high tumours. Using transfected cell lines overexpressing cyclin E, cyclin E-high and D1(high) tumours were mimicked and the cyclin D1(high) cell line normalized the cyclin E kinase activity by an induction and redirection of p21 and p27 to the cyclin E complex whereas cyclin E-high cell lines obtained increased kinase activity with out redirection or inhibitors. Based on differences in genetic aberrations as well as function of the pRb node we therefore propose a model in which cyclin D1(high) and cyclin E-high tumours represent two alternative mechanisms to inactivate the pRb pathway and thereby achieve unrestrained growth in the tumorogenesis of breast cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pRb pathway, cdk-inhibitors, cyclins, breast cancer, cell cycle, proliferation
in
Oncogene
volume
21
issue
30
pages
4680 - 4690
publisher
Nature Publishing Group
external identifiers
  • pmid:12096344
  • wos:000176625100009
  • scopus:0037063165
ISSN
1476-5594
DOI
10.1038/sj.onc.1205578
language
English
LU publication?
yes
id
1e81950f-9fdf-4ebf-9bbf-b3fd980acc6a (old id 334034)
date added to LUP
2007-11-23 12:25:44
date last changed
2017-09-03 03:44:10
@article{1e81950f-9fdf-4ebf-9bbf-b3fd980acc6a,
  abstract     = {In an attempt to identify subtypes of breast cancer and pinpoint patterns of cell cycle regulatory defects associated with clinical behaviour, proliferation and other transformation associated events, a multitude of cell cycle regulatory proteins were analysed in a material of 113 primary breast cancers. Increased proliferation was observed in two different scenarios; (1) with high cyclin D1 and elevated retinoblastoma protein (pRb) phosphorylation, (cyclin D1(high) tumours) or (2) with high cyclin E protein but low cyclin D1 and lack of corresponding pRb phosphorylation (cyclin E high tumours) indicative of an interrupted pRb pathway. Characteristic for cyclin E-high tumours were further defects in p53, p27 and bcl-2, while c-erbB2 overexpression and c-myc amplification was found in both cyclin D1(high) and E-high tumours. Using transfected cell lines overexpressing cyclin E, cyclin E-high and D1(high) tumours were mimicked and the cyclin D1(high) cell line normalized the cyclin E kinase activity by an induction and redirection of p21 and p27 to the cyclin E complex whereas cyclin E-high cell lines obtained increased kinase activity with out redirection or inhibitors. Based on differences in genetic aberrations as well as function of the pRb node we therefore propose a model in which cyclin D1(high) and cyclin E-high tumours represent two alternative mechanisms to inactivate the pRb pathway and thereby achieve unrestrained growth in the tumorogenesis of breast cancer.},
  author       = {Loden, M and Stighall, Maria and Nielsen, HN and Roos, G and Emdin, SO and Ostlund, H and Landberg, Göran},
  issn         = {1476-5594},
  keyword      = {pRb pathway,cdk-inhibitors,cyclins,breast cancer,cell cycle,proliferation},
  language     = {eng},
  number       = {30},
  pages        = {4680--4690},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node},
  url          = {http://dx.doi.org/10.1038/sj.onc.1205578},
  volume       = {21},
  year         = {2002},
}