Expression of HER family receptors and effects of anti-HER2-antibody on human myeloma cell lines.
We have recently studied expression of estrogen receptors and the growth inhibitory effects of antiestrogens on human myeloma cells. In myeloma chemotherapy, Antiestrogens in combination with other chemotherapeutic agents, may have applications in which melphalan/predonisolone still remains the standard treatment. In this study, we examined expression of HER family molecules in myeloma cells to clarify the possible usage of anti-HER2-monoclonal antibody in the treatment of myeloma. Although the mRNA levels of HER family genes analyzed by RT-PCR were significantly lower in myeloma cells than breast cancer cells, some cell lines expressed a certain amount of HER2 and HER4 proteins. In addition, an anti-HER2 monoclonal antibody, rhumAbHER2, caused significant growth inhibition in six out of eight myeloma cell lines studied and these inhibitory effects were similar to those in the breast cancer cells studied previously. The rhumAbHER2 induced up-regulation of p21 family CDK-Is (cyclin dependent kinase inhibitors) and down-regulation of VEGF genes. Moreover, combination treatment with antiestrogen had an additive growth inhibitory effect. Such analyses may provide for use of rhumAbHER2 in myeloma treatment for the future.
Otsuki
Takemi
T
Department of Hygiene, Kawasaki Medical School, Okayama 701-0192, Japan. takemi@med.kawasaki-m.ac.jp
Kurebayashi
Junichi
J
Ohkubo
Sumiko
S
Uno
Masako
M
Fujii
Tomohiro
T
Sakaguchi
Haruko
H
Hatayama
Tamayo
T
Takata
Akiko
A
Tsujioka
Takayuki
T
Sugihara
Takashi
T
Hyodoh
Fuminori
F
D000911:Antibodies, Monoclonal / Q000737:chemistry; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D018076:DNA, Complementary; D004967:Estrogens; D012313:RNA; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases