Author/Editor		Bervar, Aleš; Zajc, Irena; Sever, Nataša; Katunuma, Nobuhiko; Sloane, Bonnie F; Lah, Tamara T
Title		Invasiveness of transformed human breast epithelial cell lines is related to cathepsin B and inhibited by cysteine proteinase inhibitors
Type		članek
Source		Biol Chem
Vol. and No.		Letnik 384
Publication year		2003
Volume		str. 447-55
Language		eng
Abstract		The activities of the lysosomal cysteine proteinases cathepsin B and L are regulated by their endogenous inhibitors, stefins A and B, and cystatin C, and their imbalance may be associated with increased invasiveness and development of the malignant cell phenotype. The aim of this study was to investigate mRNA, protein and activity levels of the above proteins in relation to in vitro invasiveness and to the reported in vivo tumorigenicity of four human breast tumor cell lines: the spontaneously immortalized cell Une MCF10A, its c-Ha-ras transfectant MCF10AT, and two tumorigenic derivative cell lines, MCF10AT Ca1a and MCF10AT Ca1d. Invasiveness did not correlate with tumorigenicity, since the MCF10AT ceil was the most invasive and the remaining three were at about haff of its level. Cathepsin B expression paralleled the in vitro invasiveness through matrigel at all levels of expression, but cathepsin L did not. Stefin levels were elevated several-fold in the tumorigenic cell lines, but not in MCFIOAT. The hypothesis that cathepsin B plays an active role in the invasion of breast cancer cell lines was confirmed by the fact that synthetic cysteine proteinase inhibitors, particularly those selective for cathepsin B, significantly reduced the invasion of the MCF10AT cells.
Descriptors		BREAST NEOPLASMS CATHEPSIN B CATHEPSINS CYSTEINE PROTEINASE INHIBITORS NEOPLASM INVASIVENESS TUMOR CELLS, CULTURED RNA, MESSENGER NEOPLASM PROTEINS DNA PROBES BLOTTING, NORTHERN