Regulation Of Human Cathepsin L Expression By AAAT Repeats

Abstract

Over expression and secretion of human cathepsin L, a lysosomal cysteine protease, is one of the major determinants for the gain in metastatic ability of cancer cells. However, in humans, this protease is regulated at multiple levels. In this study, we have explored the significance of a repeat region present in its alternate promoter. Sequencing this region in seven different cancer cell lines revealed the presence of either eight or ten repeats. Cell lines with ten repeats displayed higher cathepsin L mRNA and protein expression. Further, recombinant reporter constructs containing either eight or ten repeats upstream to luciferase were transfected in cell lines to analyze their transcription regulation abilities. We observed that the construct with ten repeats resulted in higher transcription, albeit in a tissue specific manner. This is the first report demonstrating the involvement of a tandem repeat element in regulating cathepsin L expression.