Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease
| Autor: | Mary M. McCarthy, Galina Kiriakova, Dina Lev, Janet E. Price, Harriet M. Kluger, David L. Rimm, Yuval Kluger, Robert L. Camp |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Microarray Transplantation Heterologous Mice Nude Breast Neoplasms Cell Growth Processes Biology Metastasis Mice Breast cancer Predictive Value of Tests Cell Line Tumor Cell Adhesion medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis Lymph node Oligonucleotide Array Sequence Analysis Tissue microarray Gene Expression Profiling Reproducibility of Results medicine.disease Immunohistochemistry Gene expression profiling Disease Models Animal medicine.anatomical_structure Oncology Tissue Array Analysis Tumor progression Multivariate Analysis Cancer research Female Neoplasm Transplantation SLPI |
| Zdroj: | Cancer Research. 65:5578-5587 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-0108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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