PMID- 11433525
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20211203
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 31
IP  - 4
DP  - 2001 Aug
TI  - Amplification of Mycn, Ddx1, Rrm2, and Odc1 in rat uterine endometrial 
      carcinomas.
PG  - 345-56
AB  - The BDII rat is genetically predisposed to estrogen-dependent endometrial 
      adenocarcinoma and represents a valuable model for this type of tumor. Tumors 
      arising in strain crosses involving the BDII rats had previously been screened 
      for DNA copy number changes using comparative genome hybridization (CGH). It was 
      found that extra copies of the proximal region of rat chromosome (RNO) 6 commonly 
      could be detected in these tumors. Based on RH-mapping data and comparative 
      mapping with mouse and human, seven cancer-related genes were predicted to be 
      situated in RNO6q14-q16. Rat PACs were isolated for the N-myc proto-oncogene 
      (Mycn), apolipoprotein B (Apob), the DEAD box gene 1 (Ddx1), ornithine 
      decarboxylase 1 (Odc1), proopiomelanocortin (Pomc1), ribonucleotide reductase, M2 
      polypeptide (Rrm2), and syndecan 1 (Sdc1). The localization of the genes to the 
      region was verified by FISH (fluorescence in situ hybridization) mapping, and the 
      detailed order among them was determined by dual-color FISH. By Southern blot 
      analysis, it was found that the Mycn locus was highly amplified in two out of 10 
      cell cultures derived from the tumors. In one of them (designated RUT30), the 
      amplification level of Mycn was estimated at 140x. Two other genes were 
      coamplified (Ddx1 and Rrm2) at much lower levels. Similarly, in another culture 
      (designated RUT2), Mycn was amplified more than 40x, whereas three of the other 
      genes (Ddx1, Rrm2, and Odc1) were coamplified at lower levels. Using FISH on 
      metaphase chromosomes from the cell cultures analyzed, the amplified sequences 
      were shown to be located in typical HSRs. With competitive RT-PCR, distinct 
      overexpression of Mycn and Ddx1 could be demonstrated in both RUT2 and RUT30. In 
      addition, Mycn was overexpressed in two other tumors not exhibiting Mycn 
      amplification. Taken together, our results suggest that overexpression of Mycn 
      plays an important role in the development of endometrial cancer in the BDII rat. 
      In humans, Mycn amplification has been reported mainly from tumors of neuronal 
      origin. To our knowledge, this is the first report of Mycn amplification and 
      overexpression in hormone-dependent tumors.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Karlsson A
AU  - Karlsson A
AD  - Department of Cell and Molecular Biology-Genetics, Goteborg University, SE 405 30 
      Gothenburg, Sweden.
FAU - Helou, K
AU  - Helou K
FAU - Walentinsson, A
AU  - Walentinsson A
FAU - Hedrich, H J
AU  - Hedrich HJ
FAU - Szpirer, C
AU  - Szpirer C
FAU - Levan, G
AU  - Levan G
LA  - eng
SI  - GENBANK/AF222732
SI  - GENBANK/AF222733
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Chromatin)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - EC 1.17.4.- (ribonucleotide reductase M2)
RN  - EC 1.17.4.1 (Ribonucleoside Diphosphate Reductase)
RN  - EC 3.6.1.- (Ddx1 protein, rat)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
RN  - EC 3.6.4.13 (RNA Helicases)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - Animals
MH  - Chromatin/genetics
MH  - Chromosome Mapping
MH  - DEAD-box RNA Helicases
MH  - Endometrial Neoplasms/*enzymology/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Genes, myc/*genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Molecular Sequence Data
MH  - Ornithine Decarboxylase/biosynthesis/chemistry/genetics
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-myc/chemistry/genetics/isolation & purification
MH  - RNA Helicases/chemistry/genetics/isolation & purification
MH  - RNA, Messenger/biosynthesis
MH  - RNA, Neoplasm/biosynthesis
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Inbred Strains
MH  - Rats, Sprague-Dawley
MH  - Ribonucleoside Diphosphate Reductase/biosynthesis/genetics
MH  - Uterine Neoplasms/*enzymology/*genetics
EDAT- 2001/07/04 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/07/04 10:00
PHST- 2001/07/04 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/07/04 10:00 [entrez]
AID - 10.1002/gcc.1153 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2001 Aug;31(4):345-56. doi: 10.1002/gcc.1153.