Death of multiple myeloma cells induced by cAMP-signaling involves downregulation of Mcl-1 via the JAK/STAT pathway

被引：42

作者：

Follin-Arbelet, Virginie ^{[1
]}

Torgersen, Maria Lyngaas ^{[1
]}

Naderi, Elin Hallan ^{[1
]}

Misund, Kristine ^{[2
,3
]}

Sundan, Anders ^{[2
,3
]}

Blomhoff, Heidi Kiil ^{[1
]}

机构：

[1] Univ Oslo, Inst Basic Med Sci, Dept Biochem, N-0317 Oslo, Norway

[2] Norwegian Univ Sci & Technol, KG Jebsen Ctr Myeloma Res, N-7489 Trondheim, Norway

[3] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway

来源：

CANCER LETTERS | 2013年 / 335卷 / 02期

关键词：

cAMP; Multiple myeloma; JAK; STAT; Mcl-1; PROTEIN-KINASE-A; CYTOKINE SIGNALING-3; PROSTANOID RECEPTORS; CONSTITUTIVE STAT3; FORSKOLIN; SURVIVAL; TUMOR; EXPRESSION; LEUKEMIA; CANCER;

D O I：

10.1016/j.canlet.2013.02.042

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

There is a continuous search for new therapeutic targets for treatment of multiple myeloma (MM). Here we investigated the mechanisms involved in cAMP-induced apoptosis of human MM cells, cAMP-increasing agents rapidly inhibited activation of JAK1 and its substrate STAT3. In line with STAT3 being a regulator of Mcl-1 transcription, the expression of this pro-survival factor was rapidly and selectively reduced. Notably, exogenous interleukin-6 neither prevented the inhibition of JAK1/STAT3 nor the death of MM cells induced by cAMP. Our results suggest that cAMP-mediated killing of MM cells involves inhibition of the JAK/STAT pathway, making the cAMP-pathway a promising target for treatment of MM. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：323 / 331

页数：9

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