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JAM-A expression positively correlates with poor prognosis in breast cancer patients

In English

Författare

  • Elaine A. McSherry
  • Sharon F. McGee
  • Karin Jirström
  • Emma M. Doyle
  • Donal J. Brennan
  • Göran Landberg
  • Peter A. Dervan
  • Ann M. Hopkins
  • William M. Gallagher

Summary, in English

The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta 1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta 1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta 1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta 1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta 1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. (C) 2009 UICC

Publiceringsår

2009

Språk

Engelska

Sidor

1343-1351

Publikation/Tidskrift/Serie

International Journal of Cancer

Volym

125

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

John Wiley & Sons Inc.

Ämne

  • Cancer and Oncology

Nyckelord

  • junctional adhesion molecule-A
  • breast cancer
  • tight junction
  • migration

Status

Published

Forskningsgrupp

  • Pathology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 0020-7136