PMID- 12802284
OWN - NLM
STAT- MEDLINE
DCOM- 20030702
LR  - 20081121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 24
DP  - 2003 Jun 12
TI  - Metastatic lymph node 64 (MLN64), a gene overexpressed in breast cancers, is 
      regulated by Sp/KLF transcription factors.
PG  - 3770-80
AB  - MLN64, is invariably coamplified and coexpressed with erbB-2 in breast cancers. 
      The human MLN64 and ERBB2 genes are positioned at less than 50 kb from each 
      other, on chromosome 17q12. To understand the molecular basis of MLN64 
      overexpression in cancer, the genomic region containing the MLN64 and ERBB2 genes 
      was isolated and mapped. The two genes, DARPP32 and Telethonin, flanking MLN64 
      respectively on its centromeric and telomeric sides, although coamplified, are 
      not overexpressed in breast cancer cells, indicating that gene amplification is 
      not sufficient to allow overexpression. The MLN64 minimal promoter was isolated 
      and found to be a housekeeping gene promoter containing four potential Sp1 
      binding elements. Using Sp1-deficient Drosophila SL2 cells, MLN64 promoter 
      activity was induced in a dose-dependent manner by exogenous Sp1 addition. 
      Furthermore, mutation of each individual Sp1 element resulted in a significant 
      decrease in reporter gene activity, indicating that all the Sp1 binding elements 
      are functional and act together to promote gene expression. Since the ERBB2 
      promoter is also positively regulated by Sp1, this study indicates that MLN64 and 
      ERBB2 genes share common transcriptional controls together with a physical link 
      on chromosome 17q. We speculate that, in addition to the oncogenic potential of 
      erbB-2 overexpression, the unbalanced action of MLN64 contributes to the poor 
      clinical outcome of breast tumors bearing this amplified region.
FAU - Alpy, Fabien
AU  - Alpy F
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), 
      CNRS/INSERM/Universite Louis Pasteur, BP 10142, 67404 Illkirch, C.U. de 
      Strasbourg, France.
FAU - Boulay, Anne
AU  - Boulay A
FAU - Moog-Lutz, Christel
AU  - Moog-Lutz C
FAU - Andarawewa, Kumari L
AU  - Andarawewa KL
FAU - Degot, Sebastien
AU  - Degot S
FAU - Stoll, Isabelle
AU  - Stoll I
FAU - Rio, Marie-Christine
AU  - Rio MC
FAU - Tomasetto, Catherine
AU  - Tomasetto C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (STARD3 protein, human)
RN  - 0 (Sp1 Transcription Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Binding Sites
MH  - Breast Neoplasms/*genetics
MH  - CCAAT-Enhancer-Binding Protein-beta/physiology
MH  - *Carrier Proteins
MH  - Cell Line
MH  - Conserved Sequence
MH  - Female
MH  - Gene Amplification
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, erbB-2
MH  - Humans
MH  - Membrane Proteins/chemistry/*genetics
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Sp1 Transcription Factor/*physiology
EDAT- 2003/06/13 05:00
MHDA- 2003/07/03 05:00
CRDT- 2003/06/13 05:00
PHST- 2003/06/13 05:00 [pubmed]
PHST- 2003/07/03 05:00 [medline]
PHST- 2003/06/13 05:00 [entrez]
AID - 1206500 [pii]
AID - 10.1038/sj.onc.1206500 [doi]
PST - ppublish
SO  - Oncogene. 2003 Jun 12;22(24):3770-80. doi: 10.1038/sj.onc.1206500.