Differential gene expression profile in breast cancer-derived stromal fibroblasts.
BACKGROUND
Breast cancer is characterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumor-derived fibroblasts display unique phenotypic properties, it is unclear whether they also represent are a specific subpopulation.


METHODS
Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2,400 gene cDNA array. Individual gene expression pattern were confirmed by RT-PCR.


RESULTS
In a cDNA array that allows to analyze the differential gene expression of more than 2,400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2,155 genes were not significantly altered. RT-PCR performed on individual biopsies from breast cancer and normal breast tissues confirmed the validity of the pooled gene expression signature.


CONCLUSIONS
Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion.
Singer
Christian F
CF
Department of OB/GYN, Division of Special Gynecology, Medical University of Vienna, Vienna, Austria, christian.singer@meduniwien.ac.at
Gschwantler-Kaulich
Daphne
D
Fink-Retter
Anneliese
A
Haas
Cornelia
C
Hudelist
Gernot
G
Czerwenka
Klaus
K
Kubista
Ernst
E
D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000096:biosynthesis
D012333:RNA, Messenger; D014746:Vimentin; D007633:Keratins; D017493:Leukocyte Common Antigens