Biochemical and Clinical Implications of the ErbB/HER Signaling Network of Growth Factor Receptors

Klapper, Leah N.; Kirschbaum, Mark; Sela, Michael; Yarden, Yosef

doi:10.1016/s0065-230x(08)60784-8

Cited by 491 publications

(368 citation statements)

References 364 publications

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“…The intensively studied epidermal growth factor receptor (EGFR, also known as ErbB1 or HER1) is a transmembrane glycoprotein and belongs to the ErbB family of receptor tyrosine kinases together with three other homologous receptors (ErbB2-ErbB4) (1). The structure of all receptor tyrosine kinases consists of three parts: an extracellular ligand-binding domain, a transmembrane segment, and an intracellular tyrosine kinase domain with a carboxyl terminal segment.…”

Section: Introductionmentioning

confidence: 99%

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Yavas

Macháň

Wohland

2016

Biophysical Journal

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The epidermal growth factor receptor (EGFR) is a prototypical receptor tyrosine kinase involved in cell growth and proliferation and associated with various cancers. It is commonly assumed that after activation by binding of epidermal growth factor to the extracellular domain it dimerizes, followed by autophosphorylation of tyrosine residues at the intracellular domain. However, its oligomerization state before activation is controversial. In the absence of ligands, EGFR has been found in various, inconsistent amounts of monomeric, inactive dimeric, and oligomeric forms. In addition, evidence suggests that the active conformation is not a simple dimer but contains higher oligomers. As experiments in the past have been conducted at different conditions, we investigate here the influence of cell lines (HEK293, COS-7, and CHO-K1), temperature (room temperature and 37 C), and membrane localization on the quantitation of preformed dimers using SW-FCCS, DC-FCCS, quasi PIE-FCCS, and imaging FCCS. While measurement modality, temperature, and localization on upper or lower membranes have only a limited influence on the dimerization amount observed, the cell line and location to periphery versus center of the cell can change dimerization results significantly. The observed dimerization amount is strongly dependent on the expression level of endogenous EGFR in a cell line and shows a strong cell-to-cell variability even within the same cell line. In addition, using imaging FCCS, we find that dimers have a tendency to be found at the periphery of cells compared to central positions.

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Section: Introductionmentioning

confidence: 99%

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Yavas

Macháň

Wohland

2016

Biophysical Journal

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“…HER2 (synonymes: HER2/neu, ErbB2) is a receptor expressed at the surface of the cell membrane. HER2 overexpression has been observed in many human tumors of epithelial origin and has been linked with cancer development and progression (12,13). In contrast to parental NK-92, NK-92-scFv(FRP5)-zeta cells specifically and efficiently lyse HER2 expressing tumor cells of various origin and, upon coinjection, markedly delay growth of HER2 positive tumors (11).…”

Section: Introductionmentioning

confidence: 99%

In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging

Daldrup-Link

Meier

Rudelius³

et al. 2004

Eur Radiol

159

147

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“…The ERBB2 gene is also overexpressed in other cancers such as prostate, colon and pancreas cancers, and this alteration has also been considered as a negative prognosis marker by some authors (Klapper et al, 2000).…”

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confidence: 99%

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

Vernimmen¹,

Guéders²,

Pisvin

et al. 2003

Br J Cancer

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The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185 c-erbB-2 levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185 c-erbB-2 and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells.

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Biochemical and Clinical Implications of the ErbB/HER Signaling Network of Growth Factor Receptors

Cited by 491 publications

References 364 publications

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

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