Transforming activity of the lymphotoxin-beta receptor revealed by expression screening |
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Authors: | Fujiwara Shin-ichiro Yamashita Yoshihiro Choi Young Lim Wada Tomoaki Kaneda Ruri Takada Shuji Maruyama Yukio Ozawa Keiya Mano Hiroyuki |
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Affiliation: | Division of Functional Genomics, Jichi Medical School, Tochigi 329-0498, Japan. |
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Abstract: | 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. |
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Keywords: | Lymphotoxin-β receptor Pancreatic ductal carcinoma Retrovirus cDNA expression library Oncogene |
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