Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

Helena Wensman (1) , Hanna Göransson (2) , Karl-Johan Leuchowius (3) , Sara Strömberg (3) , Fredrik Pontén (3) , Anders Isaksson (2) , Gerard Roel Rutteman (4) , Nils-Erik Heldin (3) , Gunnar Pejler (1) , Eva Hellmén (1)

1 Department of Anatomy, Physiology and Biochemistry
2 Department of Medical Sciences
3 Department of Genetics and Pathology
4 Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine

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.

Mots clés: Canine mammary tumors; Mammary sarcoma; Mammary osteosarcoma; Homeobox transcription factor; Gene expression profiling; Craniofacial

Helena Wensman, Hanna Göransson, Karl-Johan Leuchowius, Sara Strömberg, Fredrik Pontén, et al.. Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas. Breast Cancer Research and Treatment, 2008, 118 (2), pp.333-343. ⟨10.1007/s10549-008-0243-7⟩. ⟨hal-00535316⟩