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

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 beta (TGF beta) family in the carcinogenesis of CMT, relative mRNA and protein expression of TGF beta-1, -2 and -3, TGF beta receptor (TGF beta R)-1 and -3, latent TGF beta-binding protein (LTBP)-1, -3 and -4, and oestrogen receptor alpha 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 beta-3, TGF beta R-3 and LTBP-4, but increased LTBP-1 expression when compared to non-neoplastic glands or adenomas. Decreased TGF beta and LTBP-4 expression were confirmed immunohistochemically. The data suggested that loss of TGF beta-3 and LTBP-4 may have growth-stimulatoiy effects in late-stage tumours, and loss of their expression, together with reduced TGF beta R-3 expression, may be associated with increased proliferative activity of CMT similar to findings in human breast cancer. (C) 2009 Elsevier Ltd. All rights reserved.