Peripheral benzodiazepine receptor antisense knockout increases tumorigenicity of MA-10 Leydig cells in vivo and in vitro

Biochemistry
G WeisingerM Gavish

Abstract

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.

References

Oct 1, 1992·Molecular and Cellular Endocrinology·M GavishR Weizman
Feb 28, 1989·European Journal of Pharmacology·J C LarcherB P Croizat
Jan 1, 1989·Annual Review of Pharmacology and Toxicology·A Verma, S H Snyder
Jan 16, 1995·European Journal of Pharmacology·A CaminsE Escubedo
May 9, 1994·Neuroreport·J OdberM R Moore
Dec 20, 1995·Biochimica Et Biophysica Acta·K E Krueger

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Citations

Aug 8, 2006·Oncogene·C Brenner, S Grimm
Jun 15, 2007·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Lena DanovichMoshe Gavish
Jul 17, 2007·Neuropharmacology·Angela Maria FalchiGiacomo Diaz
Jun 15, 2010·Structure·Vladimir M KorkhovChristopher G Tate
Jun 9, 2016·International Journal of Molecular Sciences·Leo VeenmanMoshe Gavish
Aug 21, 2019·Oral Diseases·Rafael NaglerAvishai Gavish

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