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Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues.

Publication ,  Journal Article
Wilson, KS; Roberts, H; Leek, R; Harris, AL; Geradts, J
Published in: Am J Pathol
October 2002

Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/neu-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/neu-positive and three HER2/neu-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/neu overexpressers. In HER2/neu overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/neu protein levels. In contrast, in HER2/neu overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than up-regulated (N = 19, 0.4%). Many of the differentially expressed genes have previously not been known to play a role in human neoplasia, and some of them may represent novel tumor suppressor or oncogenes. No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/neu protein levels. These included transforming acidic coiled-coil containing protein 1, glycogen phosphorylase BB, complement 1q and one EST. The differential expression of select genes was confirmed by Northern blotting (trefoil factor 3) or by immunocytochemistry (glycogen phosphorylase BB, vimentin, KAI1). In an extended validation study, 18 of 41 ER-negative, but none of 46 ER-positive, breast carcinomas were found to express vimentin, and all but one of the vimentin-positive tumors were confined to the HER2/neu-negative subgroup (P = 0.0019). Our findings support an important role of the mammary stroma in determining the clinical breast cancer phenotype.

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Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

October 2002

Volume

161

Issue

4

Start / End Page

1171 / 1185

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Polymerase Chain Reaction
  • Phenotype
  • Pathology
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Lymphatic Metastasis
  • Humans
 

Citation

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Wilson, K. S., Roberts, H., Leek, R., Harris, A. L., & Geradts, J. (2002). Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. Am J Pathol, 161(4), 1171–1185. https://doi.org/10.1016/S0002-9440(10)64394-5
Wilson, Katherine S., Helen Roberts, Russell Leek, Adrian L. Harris, and Joseph Geradts. “Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues.Am J Pathol 161, no. 4 (October 2002): 1171–85. https://doi.org/10.1016/S0002-9440(10)64394-5.
Wilson KS, Roberts H, Leek R, Harris AL, Geradts J. Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. Am J Pathol. 2002 Oct;161(4):1171–85.
Wilson, Katherine S., et al. “Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues.Am J Pathol, vol. 161, no. 4, Oct. 2002, pp. 1171–85. Pubmed, doi:10.1016/S0002-9440(10)64394-5.
Wilson KS, Roberts H, Leek R, Harris AL, Geradts J. Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. Am J Pathol. 2002 Oct;161(4):1171–1185.
Journal cover image

Published In

Am J Pathol

DOI

ISSN

0002-9440

Publication Date

October 2002

Volume

161

Issue

4

Start / End Page

1171 / 1185

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Polymerase Chain Reaction
  • Phenotype
  • Pathology
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Lymphatic Metastasis
  • Humans