Cathepsins D, B and L in Breast Carcinoma and in Transformed Human Breast Epithelial Cells (HBEC)

Abstract

An increased expression of lysosomal enzymes, cathepsin (Cat) D, Cat B and Cat L, was observed in various human tumours and after in vitro cell transformation. To establish possible co-ordination in their expression, all three cathepsins were determined in human breast tumours and in transformed human breast epithelial cells (HBEC). In breast carcinoma (n = 120) all three cathepsins, determined immunochemically and by enzymatic activity, were increased compared to normal breast tissues. The activities, correlated with the corresponding protein masses for Cat D (r = 0.77, p < 0.01), but not for Cat B and Cat L. Significant increase in Cat B activity was observed in stage II compared to stage I tumours, and Cat L activity in stage III compared to stage II tumours, but no significant correlation of cathepsin protein with tumour stage (TNM) was established. No significant correlation between Cat D and the cysteine cathepsins B and L was observed. Similarly, Cat D, Cat B and Cat L levels did not correlate in the in vitro system, e.g. in the five transformed HBEC, such as evolved after dimethylbenz(a)anthracene treatment and c-Has-ras oncogene transfection of diploid MCF-10F cell line (Calaf et al., 1993). Transformed cells showed increased anchorage-independent growth and invasive capability (MCF-10 < MCF-10FTras < D3 < D3-1 < D3-1Tras). The intracellular level of Cat D was not related to cell invasiveness, while total cellular Cat B and Cat L increased 13 fold and 4 fold, respectively, in the most invasive cell line, D3-1Tras compared to MCF-10F.(ABSTRACT TRUNCATED AT 250 WORDS)