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Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer

Lindahl, T; Landberg, Göran LU ; Ahlgren, J; Nordgren, H; Norberg, T; Klaar, S; Holmberg, L and Bergh, J (2004) In Carcinogenesis 25(3). p.375-380
Abstract
Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients... (More)
Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P < 0.0001). In p53 mutated breast cancers high cyclin E content was associated with insertions, deletions and nonsense point mutations in the p53 tumor suppressor gene, whereas low cyclin E was linked to p53 missense point mutations. We also observed statistically significant associations between a high cyclin E content and aneuploidy, high S phase, larger tumor size, estrogen receptor negativity, presence of axillary node metastases and high tumor grade. High cyclin E content was associated with poor overall survival in univariate and multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5). In summary, our findings demonstrate that overexpression of cyclin E is associated with an aggressive tumor phenotype and specific types of p53 mutations. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
25
issue
3
pages
375 - 380
publisher
Oxford University Press
external identifiers
  • pmid:14633656
  • wos:000220058900010
  • scopus:1542504200
ISSN
0143-3334
DOI
10.1093/carcin/bgh019
language
English
LU publication?
yes
id
eb59fbff-8d0e-4f16-aa54-dae102073f68 (old id 285602)
date added to LUP
2007-10-24 19:03:17
date last changed
2017-09-03 03:51:13
@article{eb59fbff-8d0e-4f16-aa54-dae102073f68,
  abstract     = {Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P &lt; 0.0001). In p53 mutated breast cancers high cyclin E content was associated with insertions, deletions and nonsense point mutations in the p53 tumor suppressor gene, whereas low cyclin E was linked to p53 missense point mutations. We also observed statistically significant associations between a high cyclin E content and aneuploidy, high S phase, larger tumor size, estrogen receptor negativity, presence of axillary node metastases and high tumor grade. High cyclin E content was associated with poor overall survival in univariate and multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5). In summary, our findings demonstrate that overexpression of cyclin E is associated with an aggressive tumor phenotype and specific types of p53 mutations.},
  author       = {Lindahl, T and Landberg, Göran and Ahlgren, J and Nordgren, H and Norberg, T and Klaar, S and Holmberg, L and Bergh, J},
  issn         = {0143-3334},
  language     = {eng},
  number       = {3},
  pages        = {375--380},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer},
  url          = {http://dx.doi.org/10.1093/carcin/bgh019},
  volume       = {25},
  year         = {2004},
}