Transforming activity of the lymphotoxin-beta receptor revealed by expression screening.
Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies. To obtain insight into the molecular pathogenesis of PDC, we constructed a retroviral cDNA expression library with total RNA isolated from the PDC cell line MiaPaCa-2. Screening of this library with the use of a focus formation assay with NIH 3T3 mouse fibroblasts resulted in the identification of 13 independent genes with transforming activity. One of the cDNAs thus identified encodes an NH(2)-terminally truncated form of the lymphotoxin-beta receptor (LTBR). The transforming activity of this short-type LTBR in 3T3 cells was confirmed by both an in vitro assay of cell growth in soft agar and an in vivo assay of tumorigenicity in nude mice. The full-length (wild-type) LTBR protein was also found to manifest similar transforming activity. These observations suggest that LTBR, which belongs to the tumor necrosis factor receptor superfamily of proteins, may contribute to human carcinogenesis.
Fujiwara
Shin-ichiro
S
Division of Functional Genomics, Jichi Medical School, Tochigi 329-0498, Japan.
Yamashita
Yoshihiro
Y
Choi
Young Lim
YL
Wada
Tomoaki
T
Kaneda
Ruri
R
Takada
Shuji
S
Maruyama
Yukio
Y
Ozawa
Keiya
K
Mano
Hiroyuki
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D020869:Gene Expression Profiling; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000737:chemistry* / Q000378:metabolism*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D009928:Organ Specificity; D019151:Peptide Library; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014018:Tissue Distribution
C505886:LTB protein, human; C505697:LTBR protein, human; C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D019151:Peptide Library; D018124:Receptors, Tumor Necrosis Factor