PMID- 18243251
OWN - NLM
STAT- MEDLINE
DCOM- 20080529
LR  - 20211203
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 640
IP  - 1-2
DP  - 2008 Apr 2
TI  - Genes encoded within 8q24 on the amplicon of a large extrachromosomal element are 
      selectively repressed during the terminal differentiation of HL-60 cells.
PG  - 97-106
LID - 10.1016/j.mrfmmm.2007.12.008 [doi]
AB  - Human acute myeloblastic leukemia HL-60 cells become resistant to differentiation 
      during long-term cultivation. After 150 passages, double minute chromosomes 
      (dmins) found in early-passaged cells are replaced by large extrachromosomal 
      elements (LEEs). In a DNA library derived from a purified fraction of LEEs, 12.6% 
      (23/183) of clones were assigned to 8q24 and 9.2% (17/183) were assigned to 14q11 
      in the human genome. Fluorescence in situ hybridization (FISH) revealed a small 
      aberrant chromosome, which had not been found in early-passaged cells, in 
      addition to the purified LEEs. We determined that each LEE consisted of six 
      discontinuous segments in a region that extended for 4.4Mb over the 8q24 locus. 
      Five genes, namely, Myc (a proto-oncogene), NSMCE2 (for a SUMO ligase), CCDC26 
      (for a retinoic acid-dependent modulator of myeloid differentiation), TRIB1 (for 
      a regulator of MAPK kinase) and LOC389637 (for a protein of unknown function), 
      were encoded by the amplicon. Breaks in the chromosomal DNA within the amplicon 
      were found in the NSMCE2 and CCDC26 genes. The discontinuous structure of the 
      amplicon unit of the LEEs was identical with that of dmins in HL-60 
      early-passaged cells. The difference between them seemed, predominantly, to be 
      the number (10-15 copies per LEE versus 2 or 3 copies per dmin) of constituent 
      units. Expression of the Myc, NSMCE2, CCDC26 and LOC389637 and TRIB1 genes was 
      constitutive in all lines of HL-60 cells and that of the first four genes was 
      repressed during the terminal differentiation of early-passaged HL-60 cells. We 
      also detected abnormal transcripts of CCDC26. Our results suggest that these 
      genes were selected during the development of amplicons. They might be amplified 
      and, sometimes, truncated to contribute to the maintenance of HL-60 cells in an 
      undifferentiated state.
FAU - Hirano, Tetsuo
AU  - Hirano T
AD  - Life Science Group, Graduate School of Integrated Arts and Sciences, Hiroshima 
      University, 1-7-1 Kagamiyama, Higashihiroshima, Hiroshima 739-8521, Japan. 
      thirano@hiroshima-u.ac.jp
FAU - Ike, Fumio
AU  - Ike F
FAU - Murata, Takehide
AU  - Murata T
FAU - Obata, Yuichi
AU  - Obata Y
FAU - Utiyama, Hiroyasu
AU  - Utiyama H
FAU - Yokoyama, Kazunari K
AU  - Yokoyama KK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071228
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
SB  - IM
MH  - Apoptosis
MH  - *Cell Differentiation
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 8
MH  - *Extrachromosomal Inheritance
MH  - *Gene Amplification
MH  - Gene Expression
MH  - Gene Library
MH  - Genomic Instability
MH  - HL-60 Cells
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Models, Genetic
MH  - Proto-Oncogene Mas
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Tagged Sites
EDAT- 2008/02/05 09:00
MHDA- 2008/05/30 09:00
CRDT- 2008/02/05 09:00
PHST- 2007/09/11 00:00 [received]
PHST- 2007/12/12 00:00 [revised]
PHST- 2007/12/13 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/05/30 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - S0027-5107(07)00431-9 [pii]
AID - 10.1016/j.mrfmmm.2007.12.008 [doi]
PST - ppublish
SO  - Mutat Res. 2008 Apr 2;640(1-2):97-106. doi: 10.1016/j.mrfmmm.2007.12.008. Epub 
      2007 Dec 28.