1. Prokineticin-1/endocrine gland-derived vascular endothelial growth factor is a survival factor for human multiple myeloma cells.
- Author
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Li, Qing-Fang, Zhu, Hai-Yan, Yang, Yue-Feng, Liu, Jiao, Xiao, Feng-Jun, Zhang, Qun-Wei, Wu, Chu-Tse, Wang, Hua, and Wang, Li-Sheng
- Subjects
ENDOCRINE glands ,VASCULAR endothelial growth factors ,MULTIPLE myeloma ,MITOGEN-activated protein kinases ,CELL lines ,APOPTOSIS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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