Co-expression of EGFRvIII with ErbB-2 enhances tumorigenesis: EGFRvIII mediated constitutively activated and sustained signaling pathways, whereas EGF-induced a transient effect on EGFR-mediated signaling pathways

@article{Yu2008CoexpressionOE,
  title={Co-expression of EGFRvIII with ErbB-2 enhances tumorigenesis: EGFRvIII mediated constitutively activated and sustained signaling pathways, whereas EGF-induced a transient effect on EGFR-mediated signaling pathways},
  author={Hong Yu and X. Gong and Xunyi Luo and W. Han and Ge Hong and Baljit Singh and Careen K. Tang},
  journal={Cancer Biology \& Therapy},
  year={2008},
  volume={7},
  pages={1818 - 1828}
}
Elevated levels of epidermal growth factor receptor (EGFR) have been detected in a variety of human cancers. Several reports have demonstrated that the Type III EGF receptor deletion-mutant (EGFRvIII) is frequently detected in various human cancers, including breast cancer. We generated and characterized monoclonal antibody against EGFRvIII. We demonstrated that 29% of DCIS, 40% of primary invasive breast cancers and 54% of metastatic lymph nodes express EGFRvIII by immunohistochemical analysis… Expand
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References

SHOWING 1-10 OF 36 REFERENCES
Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients.
TLDR
These data provide the first clinical evidence that EGFR expression is linked to activation of ErbB-2 in human breast cancers and suggest that agents targeting EGFR may be useful in the treatment of tumors with activated Erb B-2. Expand
EGFR and EGFRvIII Expression in Primary Breast Cancer and Cell Lines
TLDR
It is concluded that the expression of EGFRvIII is extremely rare in breast cancer and therefore it does not contribute to the malignant phenotype. Expand
Suppression of EGFRvIII‐mediated proliferation and tumorigenesis of breast cancer cells by ribozyme
TLDR
The results suggest that this approach has generated a tumor‐specific, biologically functional ribozyme and further demonstrate that EGFRvIII plays a significant role in breast cancer cell proliferation. Expand
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
TLDR
EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR, and the antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EG FRvIII-specific blockade. Expand
Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (‘Iressa’) is independent of EGFR expression level
TLDR
The data suggest that the antitumor activity of ZD1839 is due to a cytostatic effect, and involves apoptosis induction in a subset of sensitive cells only, and that neither MAPK nor Akt is a reliable marker of Z D1839 activity. Expand
EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations
TLDR
Almost 6% of breast carcinomas show EGFR amplification with EGFR protein overexpression and may be candidates for trials of EGFR-targeted antibodies or small inhibitory molecules. Expand
High predictive value of epidermal growth factor receptor phosphorylation but not of EGFRvIII mutation in resected stage I non-small cell lung cancer (NSCLC)
TLDR
Because pEGFR correlated with poor prognosis, it can be speculated that it plays a crucial biological role in the pathogenesis of NSCLC. Expand
Epidermal growth factor receptor vIII enhances tumorigenicity in human breast cancer.
TLDR
The studies clearly demonstrate that EGFRvIII is capable of transforming a nontumorigenic, IL-3-dependent murine hematopoietic cell line (32D cells) into an IL- 3-independent and ligand-independent malignant phenotype in vitro and in vivo. Expand
Expression of constitutively activated EGFRvlll in non‐small cell lung cancer
TLDR
Evidence is presented, for the first time, that EGFRvlll expressed in human tumors is phosphorylated and hence activated and thus EGFR vlll is a potential therapeutic target in this challenging disease. Expand
A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor
  • A. Jungbluth, E. Stockert, +12 authors L. Old
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
806 represents a category of mAbs that recognizes tumors with EGFR amplification/overexpression but not normal tissues or tumors with normal EGFR levels, and indicates that ΔEGFR is restricted to glioblastoma, in contrast to other reports that this mutation is found in tumors outside the brain. Expand
...
1
2
3
4
...