Angiogenesis, formation of new blood vessels from a preexisting vascular bed is a complex multistep process, which may also permit metastasis. The subset of patients with breast cancer demonstrating a c-erbB-2 (HER2/neu)-positive status has aggressive tumors and a poor prognosis. To investigate how tumor angiogenesis correlates with c-erbB-2 (HER2/neu) overexpression in breast carcinoma diagnos...

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side ef...

The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release are poorly understood. Here, through a functional genome-wide siRNA screen, we identify the sorting pr...

ErbB receptor tyrosine kinases (RTKs) and their ligands have important roles in normal development and in human cancer. Among the ErbB receptors only ErbB2 has no direct ligand; however, ErbB2 acts as a co-receptor for the other family members, promoting high affinity ligand binding and enhancement of ligand-induced biological responses. These characteristics demonstrate the central role of Erb...

Whether the apparent efficacy of a specific kinase inhibitor is attributable solely to inhibition of its primary target, or to combined inhibition of additional unidentified kinases, is a critical issue in cancer therapy. We used a chemical genetic approach to generate a selective inhibitor of v-erbB [a transforming allele of epidermal growth factor receptor (EGFR)] and interrogated inhibition ...

Conversion of a malignant phenotype into a more normal one can be accomplished either by down-regulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolate...

Amplification and overexpression of the erbB-2/neu protooncogene are frequently associated with aggressive clinical course of certain human adenocarcinomas, and therefore the encoded surface glycoprotein is considered a candidate target for immunotherapy. We previously generated a series of anti-ErbB-2 monoclonal antibodies (mAbs) that either accelerate or inhibit the tumorigenic growth of erbB...

BACKGROUND The 1999 WHO/IASLC histological classification of preneoplastic bronchial lesions has been shown to be reproducible, but little is known about its biological significance. The EGFR expression rate increases from normal epithelium to carcinoma in situ (CIS) with a significant difference between mild versus severe dysplasia. C-erbB-2, another member of the erbB family, is overexpressed...

Genetic damages are frequently found in both tumor and normal cells at carcinogen exposed areas in the patients with upper aerodigestive tract cancer. These phenomena are explained by the multistage process and/or field cancerization theories. The c-erbB-2 proto-oncogene has been amplified in many human tumors including breast, stomach, kidney and lung cancers. To study the possible evidence of...

Integral membrane proteins contain a hydrophobic transmembrane domain and mainly locate in the plasma membrane lipid bilayer. The receptor tyrosine kinases (RTK) of the epidermal growth factor receptor (EGFR) superfamily, including ErbB-1, ErbB-2, ErbB-3, and ErbB-4, constitute an important group of such membrane proteins, which have a profound impact on cancer initiation, progression, and pati...