期刊
LEUKEMIA & LYMPHOMA
卷 51, 期 10, 页码 1902-1912出版社
INFORMA HEALTHCARE
DOI: 10.3109/10428194.2010.512963
关键词
Multiple myeloma; prokineticin-1 (PK1)/endocrine gland-derived vascular endothelial growth factor (VEGF); Mcl-1; survival
资金
- Chinese National Basic Research and Development [2006CB504100]
- National Natural Science Foundation of China [30670885, 30900634, 30930041]
Prokineticin-1 (PK1) has been identified as a mitogen-specific protein for the endothelium of steroidogenic glands. Here we report a novel function of PK1 in the regulation of multiple myeloma (MM) cells. PK1 activates multiple signals including mitogen-activated protein kinase (MAPK), PI3K-AKT, and Jak-STAT3, sphingosine kinase-1 (SPK1) in MM cells. Treatment of MM cells with PK1 causes a time-and dose-dependent phosphorylation of MAPK, AKT and STAT3 and upregulation of SPK1 expression and cellular activity. We also show that PK1 upregulates Mcl-1 expression in a time-and dose-dependent manner in human MM cell lines and in the cells of patients with MM. Pertussis toxin, a pan-PK1 receptor inhibitor, can block PK1-induced upregulation of Mcl-1, indicating it relates to a G-protein-coupled receptor. We also show that PK1 protects MM cells against apoptosis induced by starvation for fetal calf serum (FBS), or for FBS and IL-6. Taken together, PK1 activates multiple signaling pathways and, upregulates Mcl-1 expression, leading to proliferation and survival of MM cells.
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