Two Gln187 mutants of human soluble APRIL inhibit proliferation of lung carcinoma A549 cells.

Abstract:

:Soluble APRIL (sAPRIL), the active form of a proliferation-inducing ligand (APRIL), is implicated in the proliferation of tumor cells. Suppressing APRIL function has been considered as a potential strategy for the therapy of APRIL-associated tumors. In the present study, we generated human sAPRIL and its two mutants, Gln187-D-sAPRIL (Gln187 deleted) and Gly187-sAPRIL (Gln187 replaced by Gly). In vitro experiments showed that the two mutants had similar specific binding capacity to lung carcinoma A549 cells compared to the wild-type sAPRIL, and both, especially Gly187-sAPRIL, exhibited significant antagonistic effect on sAPRIL-induced tumor cell proliferation in a dose-dependent manner, which might be predominantly mediated by blocking sAPRIL-induced MEK and ERK phosphorylation but not p38MAPK or JNK signaling. In vivo experiments with nude mice bearing A549 cell-derived xenograft tumor showed that only the Gly187-sAPRIL mutant could significantly suppress the tumor growth. These results suggest that Gln187 may be a crucial amino acid in APRIL-mediated tumor cell proliferation via the MEK-ERK signaling pathway and that the sAPRIL mutants may serve as novel potential antagonists of APRIL for the therapy of APRIL-associated cancers.

journal_name

Acta Biochim Pol

journal_title

Acta biochimica Polonica

authors

Dai S,Zheng Y,Chen B,Gao M,Zhang Y,Zhang L,Gong W,He F

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

703-10

issue

4

eissn

0001-527X

issn

1734-154X

pii

20091870

journal_volume

56

pub_type

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