טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAtir-Lande Avigail
SubjectPeripheral Benzodiazepine Receptor-Function in Cancer
of the Prostate
DepartmentDepartment of Medicine
Supervisors Professor Yeshayahu(Sha Katz
Professor Emeritus Moshe Gavish


Abstract

Benzodiazepines (Bzs) are a group of drugs. Their therapeutic effects have been correlated with their potency in binding to central BZ receptors (CBR) in the central nervous system. Benzodiazepines also bind to receptors located in various peripheral organs as well as in brain glial cells; these receptors are called “peripheral BZ receptors” (PBR). PBR are mainly located on the outer membrane of the mitochondria.

The major physiological role of PBR is still unknown but involvement of PBR was found in regulation of steroid biosynthesis, mitochondrial respiration, cancer, cellular proliferation and differentiation. Recently it was suggested that PBR play a role in the apoptosis pathway.

In the current study, we measured PBR binding in benign prostatic hyperplasia and prostate cancer tumors. PBR binding was evaluated in two fractions for each case: the fraction of the entire tissue and the mitochondrial fraction alone. The results obtained from the biopsies showed that the entire tissue fraction had higher PBR binding. Furthermore, in both fractions the binding of cancer tissues was higher than the benign tissues although not enough for statistical relevance. The ratio of entire fraction binding to mitochondrial binding was compared between the cancer and the benign tissues, and no significant difference was found, hinting that in cancer, compared to benign tissue, there is no transfer of PBR from the mitochondrial fraction to other fractions inside the cell.

Another goal of the current study was to investigate the effect of PBR on the apoptosis pathway in PC-3 cells. PBR ligands showed no effect on the apoptosis rate induced by arsenite (As2O3). In addition, arsenite didn’t influence PBR binding characteristics, suggesting that the induction of apoptosis by arsenite is not changing the binding characteristics of PBR. Another experiment conducted, tested the influence of PBR density alteration on the apoptosis rate in cells. The alteration of the PBR density was achieved by the lipofection of a plasmid expressing the full PBR cDNA. The lipofection resulted in tripling the PBR density, but the apoptosis rate was similar for cells expressing or not expressing the cDNA. Despite published evidences for different cell lines, the results of this work are not showing involvement of PBR or PBR ligands in apoptosis pathway in PC-3 cells.