Ectopic Expression of <i>MAFB</i> Gene in Human Myeloma Cells Carrying (14;20)(q32;q11) Chromosomal Translocations

Hanamura, Ichiro; Iida, Shinsuke; Akano, Yumiko; Hayami, Yoshihito; Kato, Miyuki; Miura, Kazuhisa; Harada, Shigenori; Banno, Shogo; Wakita, Atsushi; Kiyoi, Hitoshi; Naoe, Tomoki; Shimizu, Shiro; Sonta, Shin-ichi; Nitta, Masakazu; Taniwaki, Masafumi; Ueda, Ryuzo

doi:10.1111/j.1349-7006.2001.tb01142.x

Cited by 88 publications

(76 citation statements)

References 22 publications

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“…In multiple myeloma, the c-maf locus is frequently translocated to either the immunoglobulin heavy or the light chain gene, and expression is elevated, probably through an enhancer effect (Chesi et al, 1998;Bergsagel and Kuehl, 2001). Similarly, the related mafB shows elevated expression in multiple myelomas that also carry a chromosomal translocation (Hanamura et al, 2001). The small Maf proteins, MafK (Fujiwara et al, 1993), MafF (Fujiwara et al, 1993) and MafG (Kataoka et al, 1995) lack a transactivation domain.…”

Section: Introductionmentioning

confidence: 99%

MafA has strong cell transforming ability but is a weak transactivator

2003

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The maf oncogene of the avian oncogenic retrovirus AS42 encodes a nuclear bZip protein, v-Maf, that recognizes sequences related to the AP-1 target site. The corresponding cellular protein, c-Maf belongs to a family of related bZip proteins together with MafA and MafB. In this paper, we compare the transactivation and cell transforming abilities of MafA and MafB along with two forms of the c-Maf protein. These proteins induce cellular transformation when expressed in chicken embryo fibroblasts. In reporter assays, MafA is a much less effective transactivator than the other Maf proteins, but unexpectedly shows the strongest activity in cell transformation. Chimeras of MafA and MafB correlate the strong cell transforming ability of MafA with its DNA-binding domain. The DNA-binding domain of MafA is also correlated with weak transactivation. Additional mutagenesis experiments show that transactivation and transformation by MafA are also controlled by phosphorylation of two conserved serine residues in the transactivation domain. Finally, we constructed MafAestrogen receptor fusion molecules that show tightly hormone-dependent cell transforming ability. These regulatable constructs permit a kinetic characterization of target gene responses and facilitate discrimination between direct and indirect targets.

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Section: Introductionmentioning

confidence: 99%

MafA has strong cell transforming ability but is a weak transactivator

2003

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“…DNA derived from YAC clone, Y6, spanning variable region (IgVH), and those of a bacteriophage clone, Igg1-10, or BAC417p24 (BAC/PAC Resources, Oakland, CA, USA) spanning the constant region were used as probes for the IgH gene at the 14q32 locus as previously described. 13,20 Hybridization and washing protocols were the same as those available from the company (Vysis) via the Internet. Slides were counterstained with 4 0 , 6-diamino-2-phenylindole dihydrochloride (DAPI).…”

Section: Double Color Fish (Dcfish) Analysismentioning

confidence: 99%

“…9,13,20 Each PAC/BAC DNA was labeled with either Spectrum Orange or Spectrum Green with the aid of a nick translation kit (Vysis Inc., purchased through Fujisawa Pharmaceutical Co., Osaka, Japan) according to the manufacturer's instructions. DNA derived from YAC clone, Y6, spanning variable region (IgVH), and those of a bacteriophage clone, Igg1-10, or BAC417p24 (BAC/PAC Resources, Oakland, CA, USA) spanning the constant region were used as probes for the IgH gene at the 14q32 locus as previously described.…”

Section: Double Color Fish (Dcfish) Analysismentioning

confidence: 99%

“…8,9,[13][14][15][16][17][18] The ODA cell line was originally established from a female patient with IgG-type MM, but had lost its ability to secrete the M protein as a result of long-term cell culture. G-banding analysis of the ODA cells revealed a complex karyotype featuring near-tetraploidy with two or three der (14) chromosomes.…”

Section: Cell Linesmentioning

confidence: 99%

“…Recurrent aberrations include those involving the immunoglobulin heavy (IgH) and light chain (Igk and Igl) gene loci. In particular, 14q+ chromosomes, which represent rearrangements between IgH and various donor chromosomal loci, such as 11q13, 6p25, 4p16, 16q23, 8q24 and 20q11, have been suggested to play crucial roles in MM development due to deregulation of Cyclin D1, 7 MUM1/IRF4, 8,9 FGFR3, 10 c-MAF, 11 c-MYC 12 and MAFB, 13 respectively. In order to characterize the novel chromosomal translocations involved in human MM and to find the relevant proto-oncogene(s)/tumor suppressor gene(s) involved, we isolated the 1p34 breakpoint region of t(1;14)(p34;q32) found in the human MM cell line, ODA.…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma

et al. 2003

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Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sc3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosomeassociated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.

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Mature B‐ and T‐cell Neoplasms and Hodgkin Lymphoma

Siebert

2010

Cancer Cytogenetics

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Ectopic Expression of MAFB Gene in Human Myeloma Cells Carrying (14;20)(q32;q11) Chromosomal Translocations

Cited by 88 publications

References 22 publications

MafA has strong cell transforming ability but is a weak transactivator

MafA has strong cell transforming ability but is a weak transactivator

Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma

Mature B‐ and T‐cell Neoplasms and Hodgkin Lymphoma

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