Aberrant expression of BAFF receptor, a member of the tumor necrosis factor receptor family, in malignant cells of nonhematopoietic origins.
The acquired capability of evading apoptosis is one of the prerequisites for cancer development, and NF-kappaB plays a critical role by inducing anti-apoptotic molecules. In this study, we firstly carried out an expression-cloning approach to isolate the responsible molecules in the NF-kappaB activation pathway with the defective mutant cell line, COS-A717. This cell line shows reduced constitutive basal activity of NF-kappaB as compared with the parental COS cells. We successfully isolated genes with compensating activity for the pathway, and one gene encoded B-cell activating factor receptor (BAFF-R). However, a Northern blot analysis revealed that the BAFF-R expression is not only limited to cells of B cell origin, but also is found in those with nonhematopoietic origins. In the human fibrosarcoma cell line HT1080, an immunohistochemical analysis revealed that the expression of BAFF-R is not on the cell surface, but in the cytoplasm. The expression of BAFF was also detected, and the reduction of endogenous BAFF or BAFF-R by siRNA decreased the basal NF-kappaB activity. Lastly, from clinicopathological specimens, the associated expression of BAFF-R and BAFF was demonstrated in osteosarcoma. We propose that an aberrant BAFF/BAFF-R-dependent autocrine mechanism may play a role in the development of certain types of cancer cells.
Kohno
Tomoko
T
Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523 Japan.
Daa
Tsutomu
T
Otani
Hiroshi
H
Shimokawa
Isao
I
Yokoyama
Shigeo
S
Matsuyama
Toshifumi
T
D000818:Animals; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016328:NF-kappa B; C505719:TNFSF13B protein, human