Establishment and characterization of testicular cell lines from MT-PVLT-10 transgenic mice.
Males of the MT-PVLT-10 transgenic mouse line, which expresses the polyomavirus large T-antigen under the control of the metallothionein promoter, develop testicular adenomas and display seminal vesicle enlargement. Histological analysis of adenomatous testis indicates a predominance of Leydig cells, with few normal Sertoli cells or seminiferous tubules remaining. Primary cell cultures established from the testes of control nontransgenic animals (all ages) and young MT-PVLT-10 animals (before the appearance of any phenotype) quickly entered crisis and died. In contrast, permanent cell lines could be derived from pre- and postadenomatous testes from older MT-PVLT-10 mice. All primary cultures and cell lines expressed large T-antigen. A primary culture (D-37) derived from an MT-PVLT-10 male with normal testes but enlarged seminal vesicles has been maintained for over 2 years and experiments indicate that the D-37 culture is unable to form tumors in nude mice. In contrast, a primary culture (D-4) derived from adenomatous testes of an MT-PVLT-10 mouse is also immortal, but injection of this culture into nude mice consistently resulted in tumor formation. Cloning of the D-4 culture resulted in pure Sertoli or Leydig cell clones, neither of which could form tumor upon injection into nude mice. Injection of a mixture of both cell types did result in tumor formation, suggesting a dynamic interaction between these cell types in MT-PVLT-10-induced tumorigenesis.
Institut du cancer de Montréal/Centre de Recherche Louis-Charles Simard, Montréal, Québec, Canada.
M
M
Lebel
A M
AM
Mes-Masson
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis*; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D046508:Culture Techniques / Q000379:methods*; D017931:DNA Primers; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013736:Testicular Neoplasms / Q000473:pathology*; D013737:Testis / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
D000952:Antigens, Polyomavirus Transforming; D015415:Biomarkers; D017931:DNA Primers; D008668:Metallothionein