Author/Editor		Bervar, Aleš
Title		Vloga katepsinov in njihovih inhibitorjev pri razvoju raka - model celičnih linij z različno tumorigenostjo
Type		monografija
Place		Ljubljana
Publisher		Univerza v Ljubljani, Medicinska fakulteta
Publication year		2000
Volume		str. 52
Language		slo
Abstract		Biological processes involved in the progression from benign to malignant and invasive tumors are still not sufficiently understood. The availability of molecular studies involving patients (i.e. in vivo) is substantially limited by ethic, health and limited-time issues. This is the reason for the use of in vitro models immitating in vivo processes as closely as possible. Cell lines can be used as an approximation of tumors of different tumorigenicity. They are, at least in theory, stable over many generations, and can be produced in required quantities over a short period of time. In our study, we adopted an established cell line-model consisting of a parental non-tumorigenic cell line MCF10A, a ras-transfected cell line MCF10A-NeoT with low tumorigenicity (it forms pre-malignant lesions in nude mice), and of two highly in vivo tumorigenic cell lines - MCF10A-Cala and MCF10A-Cald (they were prepared from tumors formed after inoculation of nude mice with tumor cells). Our work was focused on the role of lysosomal cysteine proteinases (CatB and CatL) and their endogenous inhibitors (StA and StB) in transition from non-tumorigenic to tumorigenic cell lines. The principal role for cathepsins is supposed to be the degradation of extracellular matrix and basal membrane proteins and activation of other proteases involved in these processes. Increased concentrations of cathepsins and changes in proteinase/inhibitor equilibrium have already been correlated with worse prognosis for different tumor types. Therefore, we speculated that the levels of cathepsins and stefins correlate with cell linetumorigenicity. We compared the expression of cathepsins and stefins at mRNA, protein concentration and activity levels. Their expression and tumorigenicity in vivo were further correlated with in vitro invasiveness - the ability of cells to invade through components of extracellular matrix. (Abstract truncated at 2000 characters.)
Descriptors		CATHEPSINS BREAST NEOPLASMS TUMOR CELLS, CULTURED CYSTEINE PROTEINASE INHIBITORS NEOPLASM INVASIVENESS BREAST NEOPLASMS CATHEPSIN B GENES, RAS