Apoptosis related gene products in differentiated and tumorigenic rat Leydig cells and following regression induced by the cytotoxin ethane dimethanesulphonate.
Androgen secreting Leydig cells in the adult are differentiated with a very low turnover, however, Leydig cell tumours can arise spontaneously or after treatment with toxins. This study in the rat investigated whether changes in components of programmed cell death could be involved. In contrast to their absence in differentiated Leydig cells, antiapoptotic Bcl-2 and proapoptotic Bax were expressed in tumours. Bak and Bcl-xl were found in both tumour and normal Leydig cells. Apoptosis was induced in subcutaneous implants of Leydig cell tumour by ethane dimethanesulphonate (EDS) which is known to kill differentiated Leydig cells. The marked regression of the tumour following EDS treatment was transient and re-growth occurred between 6 and 14 days later. Tumour regression and growth was associated with a similar weight pattern in the seminal vesicles caused by changes in serum testosterone. During tumour regression, clusterin and Bax proteins were elevated but Bak, Bcl-xl and Bcl-2 were unchanged. Fas-R, Fas-L and Bax were upregulated after tumour regression had taken place. These data show that Leydig cell tumours possess many of the apoptosis related gene products and can die by apoptosis, however, regulation is clearly different in differentiated and mitotic Leydig cells.
Woolveridge
I
I
Division of Physiology, Pharmacology and Toxicology, School of Biological Sciences, Manchester University, Manchester, UK.
Taylor
M F
MF
Rommerts
F F
FF
Morris
I D
ID
D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D020287:In Situ Nick-End Labeling; D007984:Leydig Cell Tumor / Q000473:pathology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008698:Mesylates / Q000633:toxicity*; D009929:Organ Size; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013736:Testicular Neoplasms / Q000473:pathology*; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000728:Androgens; C494774:Bak1 protein, rat; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D008565:Membrane Proteins; D008698:Mesylates; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C002994:ethylene dimethanesulfonate