Ceramide galactosyltransferase (UGT8) is a molecular marker of breast cancer malignancy and lung metastases.

Abstract

Background:It was shown recently on the level of gene expression that UGT8, coding UDP-galactose:ceramide galactosyltransferase, is one of six genes whose elevated expression correlated with a significantly increased the risk of lung metastases in breast cancer patients. In this study primary tumours and their lung metastases as well as breast cancer cell lines were analysed for UGT8 expression at the protein level.Methods:Expression of UGT8 in breast cancer tissue specimens and breast cancer cell lines was analysed using IHC, real-time PCR and Western blotting.Results:Comparison of the average values of the reaction intensities (IRS scale) showed a significant difference in UGT8 expression between (1) primary and metastatic tumours (Mann–Whitney U, P<0.05), (2) tumours of malignancy grades G3 and G2 (Mann–Whitney U, P<0.01) as well as G3 and G1 (Mann–Whitney U, P<0.001) and (3) node-positive and node-negative tumours (Mann–Whitney U, P<0.001). The predictive ability of increased expression of UGT8 was validated at the mRNA level in three independent cohorts of breast cancer patients (721). Similarly, breast cancer cell lines with the ‘luminal epithelial-like’ phenotype did not express or weakly expressed UGT8, in contrast to malignant, ‘mesenchymal-like,’ cells forming metastases in nude mice.Conclusion:Our data suggest that UGT8 is a significant index of tumour aggressiveness and a potential marker for the prognostic evaluation of lung metastases in breast cancer.