Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma.
We have recently demonstrated that nuclear expression of BCL10 predicts Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue (MALT). In this study, we examined the role of B cell-activating factor of TNF family (BAFF) in mediating BCL10 nuclear translocation and HP independence of gastric DLBCL (MALT). We used immunohistochemistry and immunoblotting to measure the expression of BAFF, pAKT, BCL3, BCL10, and NF-kappaB. Transactivity of NF-kappaB was measured by electromobility shift assay. In lymphoma samples from 26 patients with gastric DLBCL (MALT), we detected aberrant expression of BAFF in 7 of 10 (70%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015). BAFF overexpression was associated with pAKT expression (P = .032), and nuclear expression of BCL3 (P = .014), BCL10 (P = .015), and NF-kappaB (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-kappaB and AKT; the activated NF-kappaB up-regulated BCL10, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 nuclear translocation, NF-kappaB transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL (MALT).
Kuo
Sung-Hsin
SH
Departments of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.
Yeh
Pei-Yen
PY
Chen
Li-Tzong
LT
Wu
Ming-Shiang
MS
Lin
Chung-Wu
CW
Yeh
Kun-Huei
KH
Tzeng
Yi-Shin
YS
Chen
Jing-Yi
JY
Hsu
Ping-Ning
PN
Lin
Jaw-Town
JT
Cheng
Ann-Lii
AL
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053264:B-Cell Activating Factor / Q000378:metabolism*; D000074018:B-Cell CLL-Lymphoma 10 Protein; D000081242:B-Cell Lymphoma 3 Protein; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D053264:B-Cell Activating Factor; D000074018:B-Cell CLL-Lymphoma 10 Protein; D000081242:B-Cell Lymphoma 3 Protein; C118591:BCL10 protein, human; C000631344:BCL3 protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt