Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3.

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Research Abstract Details 

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Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Abstract Text:

C Kawamura,M Kizaki,K Yamato,H Uchida,Y Fukuchi,Y Hattori,T Koseki,T Nishihara,Y Ikeda,

Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-beta superfamily, are a group of related proteins that are capable of inducing the formation of cartilage and bone but are now regarded as multifunctional cytokines. We show in this report a novel function of BMPs in hematopoietic cells: BMP-2 induces apoptosis not only in human myeloma cell lines (U266, RPMI 8226, HS-Sultan, IM-9, OPM-2, and KMS-12 cells), but also in primary samples from patients with multiple myeloma. The mechanism of BMP-2-induced apoptosis was investigated with the use of U266 cells, which are dependent on the interleukin-6 autocrine loop. We showed that BMP-2 caused cell-cycle arrest in the G1 phase and the subsequent apoptosis of myeloma cells. BMP-2 up-regulated the expression of cyclin-dependent kinase inhibitors (p21(CIP1/WAF1) and p27(KIP1)) and caused hypophosphorylation of retinoblastoma (Rb) protein. In studies of apoptosis-associated proteins, BMP-2 was seen to down-regulate the expression of Bcl-x(L); however, BMP-2 had no effects on the expression of Bcl-2, Bax, or Bad. Therefore, BMP-2 induces apoptosis in various human myeloma cells by means of the down-regulation of Bcl-x(L) and by cell-cycle arrest through the up-regulation of p21(CIP1/WAF1) and p27(KIP1) and by the hypophosphorylation of Rb. Further analysis showed that the signal transducer and activator of transcription 3 (STAT3) was inactivated immediately after BMP-2 treatment. We conclude that BMP-2 would be useful as a novel therapeutic agent in the treatment of multiple myeloma both by means of its antitumor effect of inducing apoptotis and through its original bone-inducing activity, because bone lesions are frequently seen in myeloma patients.

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Publishing Authors By Initials

C Kawamura,M Kizaki,K Yamato,H Uchida,Y Fukuchi,Y Hattori,T Koseki,T Nishihara,Y Ikeda,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 96

Page Numbers: 2005-11

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 15

MONTH: Sep

YEAR: 2000

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Information

Substance Name: bone morphogenetic protein 2

Registry Number: 0

Grant and Affiliation Information for Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3.

AFFILIATION: Division of Hematology, Keio University School of Medicine, Tokyo, Japan.

Country: UNITED STATES

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MEDLINETA: Blood

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