PMID- 14670176
OWN - NLM
STAT- MEDLINE
DCOM- 20040712
LR  - 20190607
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Electronic)
IS  - 1476-5586 (Linking)
VI  - 5
IP  - 5
DP  - 2003 Sep-Oct
TI  - SMAD5 gene expression, rearrangements, copy number, and amplification at fragile 
      site FRA5C in human hepatocellular carcinoma.
PG  - 390-6
AB  - Signaling by the transforming growth factor (TGF)-family members is transduced 
      from the cell surface to the nucleus by the Smad group of intracellular proteins. 
      Because we detected alterations on the long arm of chromosome 5, we examined the 
      status of the SMAD5 gene in human hepatocellular carcinoma (HCC) cell lines and 
      primary HCC. In 16 cell lines, chromosome alterations of chromosome 5 were 
      observed in nine cell lines by fluorescence in situ hybridization (FISH), and an 
      increase in SMAD5 gene copy number relative to the ploidy level was found in 
      eight lines. The breakpoints in unbalanced translocations and deletions 
      frequently occurred near the SMAD5 locus, but apparently did not cause loss of 
      SMAD5. In one cell line, where comparative genomic hybridization showed DNA copy 
      number gain confined to the region 5q31, we detected by FISH high-level 
      amplification of the SMAD5 gene located within the fragile site FRA5C. 
      Semiquantitative polymerase chain reaction did not reveal changes in SMAD5 DNA 
      levels in 15 of 17 primary HCC specimens. In 17 HCC cell lines, SMAD5 mRNA levels 
      were either maintained or upregulated by an increase in gene dosage or another 
      mechanism. Collectively, our results show that SMAD5 undergoes copy number gain 
      and increased expression, rather than loss of expression, and therefore suggest 
      that this gene does not act as a tumor-suppressor gene in HCC. The Hep-40 HCC 
      cell line with high-level amplification and significant overexpression of SMAD5 
      may be useful in studying the interaction of SMAD5 with other genes.
FAU - Zimonjic, Drazen B
AU  - Zimonjic DB
AD  - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National 
      Cancer Institute, NIH, Bethesda, MD 20892, USA.
FAU - Durkin, Marian E
AU  - Durkin ME
FAU - Keck-Waggoner, Catherine L
AU  - Keck-Waggoner CL
FAU - Park, Sang-Won
AU  - Park SW
FAU - Thorgeirsson, Snorri S
AU  - Thorgeirsson SS
FAU - Popescu, Nicholas C
AU  - Popescu NC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SMAD5 protein, human)
RN  - 0 (Smad5 Protein)
RN  - 0 (Trans-Activators)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Blotting, Northern
MH  - Blotting, Southern
MH  - Carcinoma, Hepatocellular/*genetics
MH  - Cell Line, Tumor
MH  - Cell Membrane/metabolism
MH  - Cell Nucleus/metabolism
MH  - Chromosomes/ultrastructure
MH  - DNA/ultrastructure
MH  - DNA-Binding Proteins/*biosynthesis/*genetics
MH  - Gene Deletion
MH  - Gene Dosage
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Liver Neoplasms/*genetics
MH  - Phosphoproteins/*biosynthesis/*genetics
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction
MH  - Smad5 Protein
MH  - Trans-Activators/*biosynthesis/*genetics
MH  - Translocation, Genetic
PMC - PMC1502609
EDAT- 2003/12/13 05:00
MHDA- 2004/07/13 05:00
PMCR- 2003/09/01
CRDT- 2003/12/13 05:00
PHST- 2003/12/13 05:00 [pubmed]
PHST- 2004/07/13 05:00 [medline]
PHST- 2003/12/13 05:00 [entrez]
PHST- 2003/09/01 00:00 [pmc-release]
AID - 03193 [pii]
AID - 10.1016/s1476-5586(03)80041-6 [doi]
PST - ppublish
SO  - Neoplasia. 2003 Sep-Oct;5(5):390-6. doi: 10.1016/s1476-5586(03)80041-6.