PMID- 11689290
OWN - NLM
STAT- MEDLINE
DCOM- 20011212
LR  - 20211203
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 174
IP  - 2
DP  - 2001 Dec 28
TI  - Targeting HER-2/neu-overexpressing breast cancer cells by an antisense iron 
      responsive element-directed gene expression.
PG  - 151-8
AB  - Overexpression of HER-2/neu proto-oncogene is found in many human cancers 
      including 20-30% of breast cancer and is a predictor of poor prognosis. To target 
      breast cancer cells that overexpress HER-2/neu mRNA, we previously described a 
      novel strategy that combines the principle of antisense (AS) and translational 
      inhibitory activity conferred by an iron-responsive element (IRE) (AS-IRE). Here, 
      we showed that three potential AS-IREs, i.e. AS-IRE1, 4, and 5, derived from 
      HER-2/neu antisense sequence could bind endogenous iron regulatory protein (IRP) 
      and, when placed in 5' untranslated region (5'UTR) of a reporter gene, the gene 
      expression could be translationally repressed by recombinant IRP in vitro. Using 
      AS-IRE4 as our model, we demonstrated that it is regulated by iron, and 
      importantly, such regulation is impaired in HER-2/neu-overexpressing breast 
      cancer cells. Furthermore, we showed that AS-IRE4 could preferentially direct the 
      expression of a reporter gene in HER-2/neu-overexpressing breast cancer cells. 
      Interestingly, when AS-IRE4 was placed in 5'UTR of Bax gene, a pro-apoptotic 
      protein in the Bcl-2 protein family, we observed a preferential cell killing in 
      breast cancer cells that overexpress HER-2/neu. Taken together, our results 
      suggest that AS-IRE behaves as a functional IRE and it may direct therapeutic 
      gene expression to preferentially target HER-2/neu-overexpressing breast cancer 
      cells.
FAU - Li, Z
AU  - Li Z
AD  - Department of Molecular and Cellular Oncology, The University of Texas, M. D. 
      Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
FAU - Xia, W
AU  - Xia W
FAU - Fang, B
AU  - Fang B
FAU - Yan, D H
AU  - Yan DH
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Antisense Elements (Genetics))
RN  - 0 (BAX protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Iron-Regulatory Proteins)
RN  - 0 (Iron-Sulfur Proteins)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (bcl-2-Associated X Protein)
RN  - E1UOL152H7 (Iron)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antisense Elements (Genetics)/*genetics
MH  - Breast Neoplasms/*genetics/metabolism
MH  - Consensus Sequence
MH  - DNA Primers/chemistry
MH  - Female
MH  - Gene Expression
MH  - Gene Targeting
MH  - Humans
MH  - In Vitro Techniques
MH  - Iron/metabolism
MH  - Iron-Regulatory Proteins
MH  - Iron-Sulfur Proteins/*genetics
MH  - Protein Biosynthesis
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/genetics
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - RNA, Messenger/*genetics
MH  - RNA, Neoplasm/*genetics
MH  - RNA-Binding Proteins/*genetics
MH  - Receptor, ErbB-2/*metabolism
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - bcl-2-Associated X Protein
EDAT- 2001/11/02 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/02 10:00
PHST- 2001/11/02 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/02 10:00 [entrez]
AID - S0304383501007005 [pii]
AID - 10.1016/s0304-3835(01)00700-5 [doi]
PST - ppublish
SO  - Cancer Lett. 2001 Dec 28;174(2):151-8. doi: 10.1016/s0304-3835(01)00700-5.