Signal transduction and oncogenesis by ErbB/HER receptors

Marmor, Mina D.; Skaria, Kochupurakkal Bose; Yarden, Yosef

doi:10.1016/j.ijrobp.2003.06.002

Cited by 340 publications

(278 citation statements)

References 115 publications

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“…Although both homo-and hetero-dimerization activate the EGFR network, heterodimers are found to be more potently mitogenic and HER2 heterodimers generate the strongest biological activity compared to other heterodimers. [ 20,24,32 ] TfR1 is associated with uptake of H-AFt and is more highly expressed in cancer cells compared to normal human cells. [ 12 ] It has been found that the expression of TfR1 correlates with tumor stage or cancer progression.…”

Section: Communicationmentioning

confidence: 99%

“…These receptors are activated by either homo-or heterodimerization upon ligand binding resulting in phosphorylation of specifi c tyrosine residues. [ 20,21 ] The overexpression of EGFR and HER2 in breast cancer, is associated with poor prognoses. [ 20,22,23 ] Gefi tinib is used for treatment of EGFR and HER2 overexpressing breast cancers.…”

mentioning

confidence: 99%

“…[ 20,21 ] The overexpression of EGFR and HER2 in breast cancer, is associated with poor prognoses. [ 20,22,23 ] Gefi tinib is used for treatment of EGFR and HER2 overexpressing breast cancers. [ 24,25 ] However, the therapeutic window of this drug is drastically narrowed by poor bioavailability, acquired resistance due to insuffi cient or ineffective cellular uptake and systemic toxicity resulting from interactions between drug and healthy tissue.…”

mentioning

confidence: 99%

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An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

Kuruppu

Zhang

Collins

et al. 2015

Adv Healthcare Materials

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Section: Communicationmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

Kuruppu

Zhang

Collins

et al. 2015

Adv Healthcare Materials

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“…This family is called HER (in humans) or type I RTK family [1][2]. For the majority of these receptors, binding of a ligand causes conformational changes that facilitate homo-and heterodimerisation followed by activation of the intracellular tyrosine kinase domains.…”

Section: Introductionmentioning

confidence: 99%

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Orlova

Malm

Rosestedt

et al. 2014

Eur J Nucl Med Mol Imaging

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Imaging of HER3-expressing xenografts in mice using a (99m)Tc(CO) 3-HEHEHE-Z HER3 08699 affibody molecule. Tc(CO) 3 -HEHEHE-Z 08699 was studied over time in mice bearing HER3-expressing xenografts. European Journal of Nuclear Medicine and MolecularResults. HEHEHE-Z 08699 was labeled with 99m Tc(CO) 3 with an isolated yield of >80% and a purity of >99%. Binding of 99m Tc(CO) 3 -HEHEHE-Z 08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of receptor/affibody molecule complex (70% cell associated radioactivity was internalized after 24 h). Tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor mediated uptake was also found in liver, lung, stomach, intestine, and salivary glands.At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions. The results of this study suggest feasibility of HER3-imaging in malignant tumors using affibody molecules.

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“…The human epidermal growth factor receptor 2 (HER2, also known as ErbB-2 or c-neu) plays a critical role in epidermal growth factor receptor (EGFR) family signaling Holbro and Hynes, 2004;Marmor et al, 2004). HER2 is amplified and/or overexpressed in about 20-30% of cases of human breast cancer.…”

Section: Introductionmentioning

confidence: 99%

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

et al. 2006

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We determined the impact of HER2 signaling on two proangiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), and on an antiangiogenic factor, thrombospondin-1 (TSP-1). Re-expression of HER2 in MCF-7 and T-47D breast cancer cells that endogenously express low levels of HER2 resulted in elevated expression of VEGF and IL-8 and decreased expression of TSP-1. Inhibition of HER2 with a humanized anti-HER2 antibody (trastuzumab, or Herceptin s ) or a retrovirus-mediated small interfering RNA against HER2 (siHER2) decreased VEGF and IL-8 expression, but increased TSP-1 expression in BT474 breast cancer cells that express high levels of HER2. These in vitro results were further evaluated by treatment of BT474 xenografts in immunosuppressed mice with trastuzumab. Trastuzumab inhibited growth of BT474 xenografts and decreased microvascular density associated with downregulation of VEGF and IL-8 and with upregulation of TSP-1 expression. Inhibiting the PI3K-AKT pathway decreased VEGF and IL-8 expression. AKT1 overexpession increased VEGF and IL-8 expression, but did not increase TSP-1 expression. A p38 kinase inhibitor, SB203580, instead blocked TSP-1 expression and a p38 activator, MKK6, increased TSP-1 expression. Trastuzumab stimulated sustained p38 activation and SB203580 attenuated the TSP-1 upregulation induced by trastuzumab. HER2 signaling therefore influences the equilibrium between pro-and antiangiogenic factors via distinct signaling pathways. Trastuzumab inhibits angiogenesis and tumor growth, at least in part, through activation of the HER2-p38-TSP-1 pathway and inhibition of the HER2-PI3K-AKT-VEGF/IL-8 pathway.

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Signal transduction and oncogenesis by ErbB/HER receptors

Cited by 340 publications

References 115 publications

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

An Apoferritin‐based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib

Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

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