Peripheral benzodiazepine receptor antisense knockout increases tumorigenicity of MA-10 Leydig cells in vivo and in vitro.
Peripheral benzodiazepine receptors (PBR), first described more than 20 years ago, have been attributed with many putative functions including ones in cellular proliferation and cellular respiration. Hence, it is quite conceivable that deregulation of this receptor could lead to pathology. We and others have reported the existence of PBR overexpression in different human and nonhuman malignancies, but it has never been made clear whether this aberrant malignant PBR expression is a cause or consequence of the cancer. In the current study we induced PBR underexpression by downregulating one critical subunit of the PBR complex, the isoquinoline-binding protein (IBP), using the stable antisense knockout approach, in the MA-10 Leydig cell line. Resultant clones, showing PBR deregulation, also demonstrated increased tumorigenicity, using both in vitro (loss of contact inhibition and growth in soft agar) and in vivo (increased mortality on grafting back into isogenic mice) assays. We suggest that this type of deregulation could be a later event in natural tumor progression. Consequently, PBR deregulation should be more closely studied in human malignancy.
Weisinger
Gary
G
Department of Endocrinology, Tel Aviv Sourasky Medical Center, 64239 Tel Aviv, Israel.
Kelly-Hershkovitz
Ela
E
Veenman
Leo
L
Spanier
Ilana
I
Leschiner
Svetlana
S
Gavish
Moshe
M
D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D002455:Cell Division; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D007985:Leydig Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015996:Survival Rate; D014162:Transfection
D011963:Receptors, GABA-A