PMID- 8096058
OWN - NLM
STAT- MEDLINE
DCOM- 19930420
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 13
IP  - 4
DP  - 1993 Apr
TI  - A truncated intracellular HER2/neu receptor produced by alternative RNA 
      processing affects growth of human carcinoma cells.
PG  - 2247-57
AB  - Cloned sequences encoding a truncated form of the HER2 receptor were obtained 
      from cDNA libraries derived from two HER2-overexpressing human breast cancer cell 
      lines, BT-474 and SK-BR-3. The 5' 2.1 kb of the encoded transcript is identical 
      to that of full-length 4.6-kb HER2 transcript and would be expected to produce a 
      secreted form of HER2 receptor containing only the extracellular ligand binding 
      domain (ECD). The 3' end of the truncated transcript diverges 61 nucleotides 
      before the receptor's transmembrane region, reads through a consensus splice 
      donor site containing an in-frame stop codon, and contains a poly(A) addition 
      site, suggesting that the truncated transcript arises by alternative RNA 
      processing. S1 nuclease protection assays show a 40-fold variation in the 
      abundance of the truncated 2.3-kb transcript relative to full-length 4.6-kb 
      transcript in a panel of eight HER2-expressing tumor cell lines of gastric, 
      ovarian, and breast cancer origin. Expression of this truncated transcript in 
      COS-1 cells produces both secreted and intracellular forms of HER2 ECD; however, 
      immunofluorescent labeling of HER2 ECD protein in MKN7 tumor cells that natively 
      overexpress the 2.3-kb transcript suggests that transcriptionally generated HER2 
      ECD is concentrated within the perinuclear cytoplasm. Metabolic labeling and 
      endoglycosidase studies suggest that this HER2 ECD (100 kDa) undergoes 
      differential trafficking between the endoplasmic reticulum and Golgi compartments 
      compared with full-length (185-kDa) HER2 receptor. Transfection studies indicate 
      that excess production of HER2 ECD in human tumor cells overexpressing 
      full-length HER2 receptor can result in resistance to the growth-inhibiting 
      effects of anti-HER2 monoclonal antibodies such as muMAb4D5. These findings 
      demonstrate alternative processing of the HER2 transcript and implicate a 
      potentially important growth regulatory role for intracellularly sequestered HER2 
      ECD in HER2-amplified human tumors.
FAU - Scott, G K
AU  - Scott GK
AD  - Cancer Research Institute, University of California, San Francisco 94143-0128.
FAU - Robles, R
AU  - Robles R
FAU - Park, J W
AU  - Park JW
FAU - Montgomery, P A
AU  - Montgomery PA
FAU - Daniel, J
AU  - Daniel J
FAU - Holmes, W E
AU  - Holmes WE
FAU - Lee, J
AU  - Lee J
FAU - Keller, G A
AU  - Keller GA
FAU - Li, W L
AU  - Li WL
FAU - Fendly, B M
AU  - Fendly BM
AU  - et al.
LA  - eng
GR  - CA-36773/CA/NCI NIH HHS/United States
GR  - CA-44768/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
GS  - HER2
GS  - neu
MH  - Alternative Splicing
MH  - Base Sequence
MH  - Binding Sites
MH  - *Cell Division
MH  - Cloning, Molecular
MH  - Cytoplasm/metabolism
MH  - Exons
MH  - Fluorescent Antibody Technique
MH  - Gene Expression
MH  - Genes
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides/chemistry
MH  - Polymerase Chain Reaction
MH  - Protein-Tyrosine Kinases/chemistry/*genetics/metabolism
MH  - Proto-Oncogene Proteins/chemistry/*genetics/metabolism
MH  - Proto-Oncogenes
MH  - RNA, Messenger/genetics
MH  - RNA, Neoplasm/genetics
MH  - Receptor, ErbB-2
MH  - Receptors, Cell Surface/chemistry/*genetics/metabolism
MH  - Tumor Cells, Cultured/cytology
PMC - PMC359545
EDAT- 1993/04/01 00:00
MHDA- 1993/04/01 00:01
PMCR- 1993/04/01
CRDT- 1993/04/01 00:00
PHST- 1993/04/01 00:00 [pubmed]
PHST- 1993/04/01 00:01 [medline]
PHST- 1993/04/01 00:00 [entrez]
PHST- 1993/04/01 00:00 [pmc-release]
AID - 10.1128/mcb.13.4.2247-2257.1993 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1993 Apr;13(4):2247-57. doi: 10.1128/mcb.13.4.2247-2257.1993.