Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32.3) and FGFR3 translocation

Recently several chromosomal translocations involved in myeloma cases and m yeloma cell lines; i.e., t(11;14)(q13;q32), t('8;14)(q24;q32), t(4;14)(q16. 3;q32.3), t(6;14)(p25;q32), and t(14;16)(q32.3;q23), have been identified. These translocations are considered to dysregulate genes which may be conce rned with myelomagenesis; i.e., PRAD1/ cyclin D-1, the c-myc oncogene, FGFR 3 (fibroblast growth factor receptor 3), MMSET (multiple myeloma SET domain ), MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) , and the c-maf oncogene, respectively. However, the cellular biological ro les of these genes have not yet been elucidated in myeloma cells. Because t wo of the seven human myeloma cell lines which were established at Kawasaki Medical School, Okayama, Japan, KMS-11 and KMS-18, have been proven to pos sess t(4;14)(q16.3,q32.3), we studied the expression levels of the FGFR3 ge ne in these seven cell lines and 13 primary myeloma specimens. The expressi on levels of 12 known FGF family genes (FGF-1 to 12) and 4 FGFR genes (FGFR 1 to 4) were also examined in seven cell lines. In addition, the growth sta tus of the KMS-11 and KMS-18 lines with FGF-1 or anti-FGF-4 neutralizing mo noclonal antibody (MoAb) supplementation was investigated because FGF-1 and 4 are known as the principal ligands for FGFR3. FGFR3 overexpression was o bserved in both of the cell lines possessing t(4;14)(q16.3;q32.3) and in 3 of 13 case specimens. Anti-FGF-4 neutralizing MoAb caused significant growt h inhibition in these two cell lines possessing t(4;14)(q16.3;q32.3). These findings indicate that t(4;14) (q16.3;q32.3) may provide myeloma cells wit h a growth advantage via an autocrine mechanism between FGFR3 and FGF-4.