help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2008.070988 on April 10, 2008

Published online before print April 10, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2008.070988v1
172/5/1381    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Bhati, R.
Right arrow Articles by Klauber-DeMore, N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhati, R.
Right arrow Articles by Klauber-DeMore, N.
(American Journal of Pathology. 2008;172:1381-1390.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070988

Molecular Characterization of Human Breast Tumor Vascular Cells

Rajendra Bhati*, Cam Patterson{dagger}, Chad A. Livasy{ddagger}§, Cheng Fan{ddagger}, David Ketelsen{ddagger}, Zhiyuan Hu{ddagger}, Evangeline Reynolds{ddagger}, Catherine Tanner*, Dominic T. Moore{ddagger}, Franco Gabrielli, Charles M. Perou{ddagger}§|| and Nancy Klauber-DeMore*{dagger}{ddagger}

From the Department of Surgery,* Carolina Cardiovascular Biology Center,{dagger} Lineberger Comprehensive Cancer Center,{ddagger} Department of Pathology and Laboratory Medicine,§ and Department of Genetics,|| University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Experimental Pathology and Medical Biotechnology, University of Pisa, Pisa, Italy

A detailed understanding of the assortment of genes that are expressed in breast tumor vessels is needed to facilitate the development of novel, molecularly targeted anti-angiogenic agents for breast cancer therapies. Rapid immunohistochemistry using factor VIII-related antibodies was performed on sections of frozen human luminal-A breast tumors (n = 5) and normal breast (n = 5), followed by laser capture microdissection of vascular cells. RNA was extracted and amplified, and fluorescently labeled cDNA was synthesized and hybridized to 44,000-element long-oligonucleotide DNA microarrays. Statistical analysis of microarray was used to compare differences in gene expression between tumor and normal vascular cells, and Expression Analysis Systematic Explorer was used to determine enrichment of gene ontology categories. Protein expression of select genes was confirmed using immunohistochemistry. Of the 1176 genes that were differentially expressed between tumor and normal vascular cells, 55 had a greater than fourfold increase in expression level. The extracellular matrix gene ontology category was increased while the ribosome gene ontology category was decreased. Fibroblast activation protein, secreted frizzled-related protein 2, Janus kinase 3, and neutral sphingomyelinase 2 proteins localized to breast tumor endothelium as assessed by immunohistochemistry, showing significantly greater staining compared with normal tissue. These tumor endothelial marker proteins also exhibited increased expression in breast tumor vessels compared with that in normal tissues. Therefore, these genetic markers may serve as potential targets for the development of angiogenesis inhibitors.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American Society for Investigative Pathology.