UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Effects of ErbB-2 overexpression on mitogenic signalling and cell cycle progression in human breast luminal epithelial cells
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Timms JF, White SL, O'Hare MJ, Waterfield MD
  • Publication date:
    01/11/2002
  • Pagination:
    6573, 6586
  • Journal:
    Oncogene
  • Volume:
    21
  • Issue:
    43
  • Print ISSN:
    0950-9232
  • Keywords:
    Breast, cell, Cell Cycle, CELL-CYCLE, CELLS, cycle, effects, epithelial, epithelial cell, Epithelial Cells, EPITHELIAL-CELLS, ErbB-2, luminal epithelial cells, mitogenic signalling, OVEREXPRESSION, PROGRESSION, signalling, BREAST, CELL CYCLE, Cells, Epithelial cells, CANCER, EXPRESSION, Human, London, OnCite
  • Addresses:
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK.
Abstract
Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB-2 receptor. Herein, a non- transformed, immortalized cell system was used to investigate the effects of ErbB-2 overexpression in luminal epithelial cells. The phenotypic consequence of ErbB-2 overexpression is a shortening of the G1 phase of the cell cycle and early S phase entry, which leads to hyperproliferation. We show that this effect was mediated through the up-regulation of cdk6 and cyclins D1 and E, and enhanced degradation and relocalization of p27(Kip1). These changes were effected predominantly through enhanced MAPK signalling, resulting in cdk2 hyperactivation. PI3K signalling also participated in cell cycle progression, since PI3K and MAPK coordinately regulated changes in cyclin D1 and cdk6 expression. Cdk4 activity was not required for cell cycle progression in these cells, and was constitutively inhibited through its association with p16(INK4A). MAPK-dependent induction of p21(Cip1) was also necessary for G1 phase progression, although its degradation by the proteasome was required for S phase entry. These data provide new insights into the complex molecular mechanisms underlying mitogenic cell cycle control in luminal epithelial cells, the cell type relevant to primary breast cancer, and show how ErbB-2 overexpression subverts this normal control. doi:10.1038/sj.onc.1205847
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Department of Surgical Biotechnology
Author
Div of Biosciences
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by