Using a xenograft model of human breast cancer metastasis to find genes associated with clinically aggressive disease

Harriet M. Kluger, Dina Chelouche Lev, Yuval Kluger, Mary M. McCarthy, Galina Kiriakova, Robert L. Camp, David L. Rimm, Janet E. Price*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Metastasis is the primary cause of death from breast cancer. A xenograft model was used to identify genes potentially involved with metastasis, comparing expression in the poorly metastatic GI101A human breast cancer cell line and a highly metastatic variant, GILM2. cDNA microarray analyses of these isogenic variants were done using 16K Operon 70-mer oligonucleotide microarray slides. Differentially expressed genes were identified by ANOVA, and differences of ≥2.5-fold were found for 106 genes. Changes in protein or RNA expression were confirmed for 10 of 12 genes. Three markers, heat shock protein 70 (HSP-70), chemokine (C-X-C motif) ligand 1 (CXCL-1), and secreted leukocyte protease inhibitor (SLPI), were studied further with breast cancer tissue microarrays using a novel method of automated quantitative analysis. This uses cytokeratin to define pixels as breast cancer (tumor mask) within the tissue array spot and then measures intensity of marker expression using a cyanine 5-conjugated antibody within the mask. Scores were correlated with clinicopathologic variables. High HSP-70 expression and high nuclear CXCL-1 expression in primary tumors were both associated with decreased survival (P = 0.05 and 0.027, respectively). Expression of each marker was strongly associated with lymph node involvement (P = 0.0002, 0.008, 0.0012, and 0.012 for HSP-70, nuclear CXCL-1, cytoplasmic CXCL-1, and SLPI, respectively). Identification of genes associated with metastasis in experimental models may have clinical implications for the management of breast cancer, because some of these are associated with lymph node metastasis and survival and might be useful as prognostic markers or molecular targets for novel therapies.

Original languageEnglish
Pages (from-to)5578-5587
Number of pages10
JournalCancer Research
Issue number13
StatePublished - 1 Jul 2005
Externally publishedYes


FundersFunder number
National Cancer InstituteP30CA016672, R21CA100825
National Institute of Diabetes and Digestive and Kidney DiseasesU24DK058776
National Institute of Environmental Health SciencesK08ES011571


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