Unknown,Transcriptomics,Genomics,Proteomics

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MPA-induced gene expression and stromal and parenchymal gene expression profiles in luminal murine mammary tumors with different hormonal requirements


ABSTRACT: Introduction: Over the past several years, we have been interested in understanding the mechanisms by which hormone-dependent (HD) mammary carcinomas grow in the absence of the stimulatory hormone. We have hypothesized that the stromal compartment plays a pivotal role in the acquisition of the hormone-independent (HI) phenotype by providing stimulatory factors that replace the proliferative effects of the hormone. Methods: We used DNA microarrays to compare the gene expression profiles of tumors from the MPA mouse breast cancer model, one hormone-dependent (C4-HD) and one hormone-independent (C4-HI), using whole tumor samples or laser-captured purified stromal and epithelial cells obtained from the same tumors. The expression of selected genes was validated by immunohistochemistry and immunofluorescence assays. Results: We identified 413 genes that were expressed in tumor stroma but not in epithelial cells. Eighty-five percent of these genes were upregulated, whereas the remaining 15% were downregulated in C4-HI tumors relative to their expression in the C4-HD tumor stroma. Several matrix metallopeptidases, including Mmp13, Mmp3, Mmp10 and Mmp9, were overexpressed in the C4-HI tumor microenvironment. On the other hand, 1100 genes were specifically expressed in the tumor parenchyma. Among them, the 29% were upregulated, whereas the remaining 71% were downregulated, in C4-HI relative to C4-HD tumor epithelium. Steap, Pdgfc, Runx2, Cxcl9 and Sdf2 were among the genes with high expression in the C4-HI tumor parenchyma. Interestingly, we found that Fgf2 was one of the few genes upregulated by MPA in C4-HD tumors, confirming its pivotal role in regulating tumor growth in this model. Conclusions: We demonstrate a gene expression profile that distinguishes epithelial from stromal cells in mammary tumors with different hormone dependence. Our results support the hypothesis that the tumor-associated stroma may contribute to hormone-independent tumor growth. The fact that Fgf2 was one of these few stimulatory genes is worth investigating. reference X sample

ORGANISM(S): Mus musculus

SUBMITTER: Charles Perou 

PROVIDER: E-GEOD-23214 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MPA-induced gene expression and stromal and parenchymal gene expression profiles in luminal murine mammary carcinomas with different hormonal requirements.

Giulianelli Sebastián S   Herschkowitz Jason I JI   Patel Vyomesh V   Lamb Caroline A CA   Gutkind J Silvio JS   Molinolo Alfredo A   Perou Charles M CM   Lanari Claudia C  

Breast cancer research and treatment 20101002 1


Over the past several years, we have been interested in understanding the mechanisms by which mammary carcinomas acquire hormone independence. We demonstrated that carcinoma associated fibroblasts participate in the ligand-independent activation of progesterone receptors inducing tumor growth. In this study, we used DNA microarrays to compare the gene expression profiles of tumors from the MPA mouse breast cancer model, one hormone-dependent (C4-HD) and one hormone-independent (C4-HI), using who  ...[more]

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