IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
MPA-induced gene expression and stromal and parenchymal gene expression profiles in luminal murine mammary carcinomas with different hormonal requirements
Autor/es:
GIULIANELLI S; HERSCHKOWITZ J; PATEL V; LAMB CA; GUTKIND JS; MOLINOLO AA; PEROU C; LANARI C
Revista:
BREAST CANCER RESEARCH AND TREATMENT
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2011 vol. 129 p. 49 - 67
ISSN:
0167-6806
Resumen:
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 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. We identified 413 genes specifically expressed intumor stroma. Eighty-five percent of these genes were
upregulated, whereas the remaining 15% were downregulated
in C4-HI relative to their expression in the C4-HD
tumor stroma. Several matrix metallopeptidases 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,
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. In conclusion, we demonstrate
herein a gene expression profile that distinguishes both the
epithelial and the stromal cells in mammary tumors with
different hormone dependence, supporting the hypothesis
that the tumor-associated stroma may contribute to hormone-
independent tumor growth.