PMID- 15735670
OWN - NLM
STAT- MEDLINE
DCOM- 20050603
LR  - 20240312
IS  - 0950-9232 (Print)
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 21
DP  - 2005 May 12
TI  - Expression of EGF-family receptors and amphiregulin in multiple myeloma. 
      Amphiregulin is a growth factor for myeloma cells.
PG  - 3512-24
AB  - A hallmark of plasma cells is the expression of syndecan-1, which has major 
      functions in epithelial cells, in particular as the coreceptor of heparin-binding 
      growth factors. We previously found that heparin-binding epidermal growth 
      factor-like growth factor (HB-EGF) is a growth factor for malignant plasma cells. 
      As amphiregulin (AREG) is another heparin-binding factor of the EGF family, we 
      investigated its role in multiple myeloma (MM). Using Affymetrix DNA microarrays, 
      we show here that the AREG gene was expressed by purified primary myeloma cells 
      from 65 patients and that the expression was higher than in normal bone marrow 
      (BM) plasma cells or plasmablastic cells. AREG stimulated IL-6 production and 
      growth of BM stromal cells. Using real-time reverse transcriptase-polymerase 
      chain reaction, we found that MM cells expressed ErbB receptors and that AREG 
      promoted their growth. Furthermore, PD169540 (a pan-ErbB inhibitor) and IRESSA 
      (an ErbB1-specific inhibitor) induced apoptosis of primary myeloma cells from 
      10/14 and 4/14 patients, respectively, and there was a synergistic effect with 
      dexamethasone. Altogether, our data provide strong evidence that AREG plays an 
      important role in the biology of MM and emphasize the advantages of using ErbB 
      inhibitors, which might target myeloma cells as well as the tumor environment.
FAU - Mahtouk, Karene
AU  - Mahtouk K
AD  - INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, Hopital St Eloi, 
      34000 Montpellier, France.
FAU - Hose, Dirk
AU  - Hose D
FAU - Reme, Thierry
AU  - Reme T
FAU - De Vos, John
AU  - De Vos J
FAU - Jourdan, Michel
AU  - Jourdan M
FAU - Moreaux, Jerome
AU  - Moreaux J
FAU - Fiol, Genevieve
AU  - Fiol G
FAU - Raab, Marc
AU  - Raab M
FAU - Jourdan, Eric
AU  - Jourdan E
FAU - Grau, Veronique
AU  - Grau V
FAU - Moos, Marion
AU  - Moos M
FAU - Goldschmidt, Hartmut
AU  - Goldschmidt H
FAU - Baudard, Marion
AU  - Baudard M
FAU - Rossi, Jean Francois
AU  - Rossi JF
FAU - Cremer, Friedrich W
AU  - Cremer FW
FAU - Klein, Bernard
AU  - Klein B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Amphiregulin
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Bone Marrow Cells
MH  - Cell Proliferation
MH  - EGF Family of Proteins
MH  - ErbB Receptors/antagonists & inhibitors/*physiology
MH  - Gefitinib
MH  - *Gene Expression Profiling
MH  - Glycoproteins/*biosynthesis/*genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis/*genetics
MH  - Multiple Myeloma/*genetics/*physiopathology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Plasma Cells/physiology
MH  - Quinazolines/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2408676
MID - HALMS130206
OID - NLM: HALMS130206
EDAT- 2005/03/01 09:00
MHDA- 2005/06/04 09:00
PMCR- 2008/06/06
CRDT- 2005/03/01 09:00
PHST- 2005/03/01 09:00 [pubmed]
PHST- 2005/06/04 09:00 [medline]
PHST- 2005/03/01 09:00 [entrez]
PHST- 2008/06/06 00:00 [pmc-release]
AID - 1208536 [pii]
AID - 10.1038/sj.onc.1208536 [doi]
PST - ppublish
SO  - Oncogene. 2005 May 12;24(21):3512-24. doi: 10.1038/sj.onc.1208536.