The ErbB RTKs (EGFR, HER2, HER3, and HER4) have been well-studied in cancer. EGFR, HER3 stimulate cancer proliferation, principally by activating the phosphatidylinositol-3-kinase extracellular signal-regulated kinase (ERK) pathways, resulting increased cell survival proliferation. Cancer cells high densities of causing phosphorylation tyrosine amino acids on protein substrates near C-terminal ...

Bidirectional cross talk between members of the human epidermal growth factor family of receptors (HER) and the estrogen receptor (ER) is believed to underlie resistance mechanisms that develop in response to treatment with anti-HER agents and endocrine therapy. We investigated the interaction between HER2, HER3 and the ER in vitro using human embryonic kidney cells transfected with human HER2,...

Heterodimerization of human epidermal growth factor receptor 2 (HER2) with HER3 initiates aberrant downstream growth-signaling pathways in tumors. Our objective was to construct bispecific radioimmunoconjugates (bsRICs) that recognize HER2 and evaluate their ability image tumors athymic mice express one or both receptors using small-animal SPECT/CT. Methods: bsRICs were constructed by re...

In teleosts and amphibians, the proneuronal domains, which give rise to primary-motor, primary-inter and Rohon-Beard (RB) neurons, are established at the beginning of neurogenesis as three longitudinal stripes along the anteroposterior axis in the dorsal ectoderm. The proneuronal domains are prefigured by the expression of basic helix-loop-helix (bHLH) proneural genes, and separated by domains ...

We previously showed that tumor-derived heregulin, a ligand for HER3, is associated with both de novo and acquired resistance to cetuximab. We have now examined whether patritumab, a novel neutralizing monoclonal antibody to HER3, is able to overcome such resistance. Human colorectal cancer (DiFi) cells that are highly sensitive to cetuximab were engineered to stably express heregulin by retrov...

Blockade of the human epidermal growth factor receptor 3 (HER3) and of the downstream phosphatidylinositide 3-kinase (PI3K)/AKT pathway is a prerequisite for overcoming drug resistance and to develop novel treatments for cancers that are not eligible for the currently approved targeted therapies. To this end, we generated specific antibodies (Abs) against domain 1 (D1) and domain 3 (D3) of HER3...

HER2-targeted therapies have radically changed the prognosis of HER2-positive breast cancer over the last few years. However, resistance to these therapies has been a constant, leading to treatment-failure and new tumor progression. Recently, the kinase-impaired HER3 emerged as a pivotal player in oncogenic signaling, with an important role in both non-treated progression and treatment response...

The HER family of receptor tyrosine kinases, including EGF receptor (EGFR), HER2, HER3, and HER4, transduce growth-promoting signals in response to ligand binding to their extracellular domains (ECD). This family is deregulated in numerous cancers, withmutations in EGFR andHER2 often serving as "driver" events to activate key growth factor signaling pathways such as the RAS-ERK and PI3K-AKT pat...

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric c...

Neuregulin-1 (NRG-1), binding to the human epidermal growth factor receptor HER2/HER3, plays a role in pulmonary epithelial cell proliferation and recovery from injury in vitro. We hypothesized that activation of HER2/HER3 by NRG-1 would also play a role in recovery from in vivo lung injury. We tested this hypothesis using bleomycin lung injury of transgenic mice incapable of signaling through ...