Establishment and characterization of renal carcinoma cell lines from a Bhd gene mutant (Nihon) rat.
A germline insertion of a single nucleotide in the rat homologue of the human Birt-Hogg-Dubé (BHD) gene gives rise to dominantly inherited renal cell carcinoma (RCC) in the Nihon rat model. In this study, we established 7 lines (NR cell lines NR22, 24, 32, 45, 49, 54 and 64) from an RCC found in a Nihon rat. All cell lines consisted mainly of round or polygonal cells arranged in a cobblestone-like growth pattern. Cells of NR cell lines had abundant cytoplasm and tight junctions as well as microvilli on electron microscopy and were positive for cytokeratin on immunocytochemistry. Cell lines NR22, 24 and 32 showed rapid growth, whereas the growth of the remaining lines was very slow. While the modal chromosome number of lines NR24, 45 and 54 was 42, the remaining lines exhibited aberrant modal numbers ranging from 70 to 96. All NR cell lines formed tumors at subcutaneous inoculation sites in nude mice, and tumors from lines NR54 and 64 developed pulmonary metastases. All NR cell lines had a germline mutation in the rat Bhd gene in the gene analysis. NR cell lines would prove valuable experimental tools for studies on unique functions of the Bhd gene and renal carcinogenesis.
Matsumoto
Izumi
I
Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan. izumi-matsumoto@ds-pharma.co.jp
Kouchi
Mami
M
Okimoto
Kazuo
K
Kijima
Kazuyasu
K
Ueda
Tadayoshi
T
Hirayama
Youko
Y
Inoue
Tadashi
T
Seki
Takaki
T
Hino
Okio
O
D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D005260:Female; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D008871:Microvilli / Q000648:ultrastructure; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D019108:Tight Junctions / Q000648:ultrastructure; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014746:Vimentin / Q000032:analysis
C526060:Bhd protein, mouse; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D014746:Vimentin; D007633:Keratins