Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas.
The global gene expression in three types of canine mammary tumors: carcinoma, fibrosarcoma and osteosarcoma were investigated by Affymetrix gene array technology. Unsupervised clustering analysis revealed a close clustering of the respective tumor types, with fibrosarcomas clustering close to the osteosarcomas and the carcinomas clustering closer to non-malignant mammary tissues (NMTs). A number of epithelial markers were expressed in both carcinomas and NMTs, whereas the sarcomas expressed genes related to mesenchymal differentiation. A comparison of the gene expression profile of the sarcomas versus carcinoma/NMTs revealed that the sarcomas, in particular the osteosarcomas, showed a striking upregulation of a panel of homeobox genes previously linked to craniofacial bone formation. In line with this finding, osteosarcomas showed an upregulation of bone morphogenetic proteins (BMPs) and of genes associated with retinoic acid signaling. Increased homeobox gene expression in sarcomas was also confirmed at the protein level by immunohistochemical analysis of tumor tissue, and in an osteosarcoma cell line after stimulation by BMP-2. These findings suggest that the development of mammary sarcomas specifically involves triggering of a set of homeobox genes related to neural crest and craniofacial bone development.
Wensman
Helena
H
Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, P.O.Box 7011, 750 07, Uppsala, Sweden. Helena.Wensman@afb.slu.se
Göransson
Hanna
H
Leuchowius
Karl-Johan
KJ
Strömberg
Sara
S
Pontén
Fredrik
F
Isaksson
Anders
A
Rutteman
Gerard Roel
GR
Heldin
Nils-Erik
NE
Pejler
Gunnar
G
Hellmén
Eva
E
D000818:Animals; D016000:Cluster Analysis; D004283:Dog Diseases; D004285:Dogs; D005147:Facial Bones; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D005801:Genes, Homeobox / Q000235:genetics*; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000235:genetics*; D012886:Skull