Search results

Sort By:

Limit search:

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

100%

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

issue 4

703-710

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.

Refine search results

1 Acta Biochimica Polonica

1 2009

1 Chen B.

1 Dai S.

1 Gao M.

1 Gong W.

1 He F.

1 Zhang L.

1 Zhang Y.

1 Zheng Y.

Search results

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