- Tytuł:
- Two Gln187 mutants of human soluble APRIL inhibit proliferation of lung carcinoma A549 cells
- Autorzy:
-
Dai, Shuangshuang
Zheng, Yingru
Chen, Bin
Gao, Min
Zhang, Yan
Zhang, Li
Gong, Wei
He, Fengtain - Powiązania:
- https://bibliotekanauki.pl/articles/1040492.pdf
- Data publikacji:
- 2009
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
APRIL
Gln187 mutant of sAPRIL
anti-tumor activity - Opis:
- 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.
- Źródło:
-
Acta Biochimica Polonica; 2009, 56, 4; 703-710
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł