Alterations in vascular gene expression in invasive breast carcinoma

Belinda S. Parker, Pedram Argani, Brian P. Cook, Han Liangfeng, Scott D. Chartrand, Mindy Zhang, Saurabh Saha, Alberto Bardelli, Yide Jiang, Thia B. St. Martin, Mariana Nacht, Beverly A. Teicher, Katherine W. Klinger, Saraswati Sukumar, Stephen L. Madden

Research output: Contribution to journalArticle

Abstract

The molecular signature that defines tumor microvasculature will likely provide dues as to how vascular-dependent tumor proliferation is regulated. Using purified endothelial cells, we generated a database of gene expression changes accompanying vascular proliferation in invasive breast cancer. In contrast to normal mammary vasculature, invasive breast cancer vasculature expresses extracellular matrix and surface proteins characteristic of proliferating and migrating endothelial cells. We define and validate the up-regulated expression of VE-cadherin and osteonectin in breast tumor vasculature. In contrast to other tumor types, invasive breast cancer vasculature induced a high expression level of specific transcription factors, including SNAIL1 and HEYL, that may drive gene expression changes necessary for breast tumor neovascularization. We demonstrate the expression of HEYL in tumor endothelial cells and additionally establish the ability of HEYL to both induce proliferation and attenuate programmed cell death of primary endothelial cells in vitro. We also establish that an additional intracellular protein and previously defined metastasis-associated gene, PRL3, appears to be expressed predominately in the vasculature of invasive breast cancers and is able to enhance the migration of endothelial cells in vitro. Together, our results provide unique insights into vascular regulation in breast tumors and suggest specific roles for genes in driving tumor angiogenesis.

Original languageEnglish
Pages (from-to)7857-7866
Number of pages10
JournalCancer Research
Volume64
Issue number21
DOIs
Publication statusPublished - Nov 1 2004

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Parker, B. S., Argani, P., Cook, B. P., Liangfeng, H., Chartrand, S. D., Zhang, M., Saha, S., Bardelli, A., Jiang, Y., St. Martin, T. B., Nacht, M., Teicher, B. A., Klinger, K. W., Sukumar, S., & Madden, S. L. (2004). Alterations in vascular gene expression in invasive breast carcinoma. Cancer Research, 64(21), 7857-7866. https://doi.org/10.1158/0008-5472.CAN-04-1976