Advanced

Down-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features.

Lehn, Sophie LU ; Tobin, Nicholas P LU ; Berglund, Pontus LU ; Nilsson, Kristina LU ; Sims, Andrew H; Jirström, Karin LU ; Härkönen, Pirkko LU ; Lamb, Rebecca and Landberg, Göran LU (2010) In American Journal of Pathology 177. p.2886-2897
Abstract
The oncogene cyclin D1 is highly expressed in many breast cancers and, despite its proliferation-activating properties, it has been linked to a less malignant phenotype. To clarify this observation, we focused on two key components of malignant behavior, migration and proliferation, and observed that quiescent G0/G1 cells display an increased migratory capacity compared to cycling cells. We also found that the down-regulation of cyclin D1 in actively cycling cells significantly increased migration while also decreasing proliferation. When analyzing a large set of premenopausal breast cancers, we observed an inverse proliferation-independent link between cyclin D1 and tumor size and recurrence, suggesting that this protein might abrogate... (More)
The oncogene cyclin D1 is highly expressed in many breast cancers and, despite its proliferation-activating properties, it has been linked to a less malignant phenotype. To clarify this observation, we focused on two key components of malignant behavior, migration and proliferation, and observed that quiescent G0/G1 cells display an increased migratory capacity compared to cycling cells. We also found that the down-regulation of cyclin D1 in actively cycling cells significantly increased migration while also decreasing proliferation. When analyzing a large set of premenopausal breast cancers, we observed an inverse proliferation-independent link between cyclin D1 and tumor size and recurrence, suggesting that this protein might abrogate infiltrative malignant behavior in vivo. Finally, gene expression analysis after cyclin D1 down-regulation by siRNA confirmed changes in processes associated with migration and enrichment of our gene set in a metastatic poor prognosis signature. This novel function of cyclin D1 illustrates the interplay between tumor proliferation and migration and may explain the attenuation of malignant behavior in breast cancers with high cyclin D1 levels. (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
American Journal of Pathology
volume
177
pages
2886 - 2897
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000285369800023
  • pmid:20971731
  • scopus:78650224628
ISSN
1525-2191
DOI
10.2353/ajpath.2010.100303
language
English
LU publication?
yes
id
efcf5f6c-f2a6-403f-93cc-64241f5a8f27 (old id 1710817)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20971731?dopt=Abstract
date added to LUP
2010-11-05 13:57:59
date last changed
2018-06-10 04:47:35
@article{efcf5f6c-f2a6-403f-93cc-64241f5a8f27,
  abstract     = {The oncogene cyclin D1 is highly expressed in many breast cancers and, despite its proliferation-activating properties, it has been linked to a less malignant phenotype. To clarify this observation, we focused on two key components of malignant behavior, migration and proliferation, and observed that quiescent G0/G1 cells display an increased migratory capacity compared to cycling cells. We also found that the down-regulation of cyclin D1 in actively cycling cells significantly increased migration while also decreasing proliferation. When analyzing a large set of premenopausal breast cancers, we observed an inverse proliferation-independent link between cyclin D1 and tumor size and recurrence, suggesting that this protein might abrogate infiltrative malignant behavior in vivo. Finally, gene expression analysis after cyclin D1 down-regulation by siRNA confirmed changes in processes associated with migration and enrichment of our gene set in a metastatic poor prognosis signature. This novel function of cyclin D1 illustrates the interplay between tumor proliferation and migration and may explain the attenuation of malignant behavior in breast cancers with high cyclin D1 levels.},
  author       = {Lehn, Sophie and Tobin, Nicholas P and Berglund, Pontus and Nilsson, Kristina and Sims, Andrew H and Jirström, Karin and Härkönen, Pirkko and Lamb, Rebecca and Landberg, Göran},
  issn         = {1525-2191},
  language     = {eng},
  pages        = {2886--2897},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Down-Regulation of the Oncogene Cyclin D1 Increases Migratory Capacity in Breast Cancer and Is Linked to Unfavorable Prognostic Features.},
  url          = {http://dx.doi.org/10.2353/ajpath.2010.100303},
  volume       = {177},
  year         = {2010},
}