Downregulation of transforming growth factor (TGF) and latent TGF binding protein (LTBP)-4 expression in late stage canine mammary tumours.

摘要

Although canine mammary tumours (CMT) are the most common malignant tumours in bitches the pathogenesis is far from understood. To analyse the role of the transforming growth factor (TGF) family in the carcinogenesis of CMT, relative mRNA and protein expression of TGF-1, -2 and -3, TGF receptor (TGFR)-1 and -3, latent TGF-binding protein (LTBP)-1, -3 and -4, and oestrogen receptor in CMT were quantified. mRNA expression concentrations were measured in laser-microdissected tissue samples of mammary adenomas, carcinomas and their lymph node metastases and normalised to the non-neoplastic mammary gland of the same dog. Carcinomas and metastases had significantly decreased expression levels of TGF-3, TGFR-3 and LTBP-4, but increased LTBP-1 expression when compared to non-neoplastic glands or adenomas. Decreased TGF and LTBP-4 expression were confirmed immunohistochemically. The data suggested that loss of TGF-3 and LTBP-4 may have growth-stimulatory effects in late-stage tumours, and loss of their expression, together with reduced TGFR-3 expression, may be associated with increased proliferative activity of CMT similar to findings in human breast cancer.