<i>Flow Cytometric FRET Analysis of erbB Receptor Interaction on a Cell‐by‐Cell Basis</i>

Diermeier-Daucher, Simone; Hasmann, Max; Brockhoff, Gero

doi:10.1196/annals.1430.003

Cited by 18 publications

(20 citation statements)

References 28 publications

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“…1A and 1B) (3). Strikingly, Pertuzumab but not Trastuzumab was highly efficient in inhibition/reduction of Her2/ Her3 hetero- (42) and Her2 homodimerization (19). Hence, a shift in the ErbB receptor interaction pattern caused by HRG that compensates for the inhibitory effect of Lapatinib may efficiently be counteracted by Pertuzumab rather than by Trastuzumab.…”

Section: Hrg-caused Compensation Of Lapatinib Treatment Is Efficientlmentioning

confidence: 93%

“…An enhanced antiproliferative effect generated by combined tumor-cell targeting has been explained by different but complementing mechanisms of action of anti-ErbB receptor antibodies and TKIs. Because of different epitope recognition (18), the Her2-specific antibodies Trastuzumab and Pertuzumab differentially affect Her2 receptor interaction and crossactivation (8), which has been suggested to synergistically inhibit tumor-cell growth (19). The Lapatinib-TKI, however, has been developed rather to reversibly inhibit kinase activity of both the Her2 and the epidermal growth factor receptor (EGFR; 20,21).…”

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confidence: 99%

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Modular anti‐EGFR and anti‐Her2 targeting of SK‐BR‐3 and BT474 breast cancer cell lines in the presence of ErbB receptor‐specific growth factors

et al. 2011

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Over the last decade, a number of monoclonal antibodies and small molecule inhibitors emerged as potent therapeutic agents in the treatment of Her2/neu overexpressing breast cancer. Numerous patients, however, do not adequately respond to anti-epidermal growth factor receptor (EGFR)/Her2 receptor targeting. Receptor-and, in turn, growth-stimulating effects, which potentially hamper antiproliferative cell treatment, have barely been investigated. BT474 and SK-BR-3 breast cancer cell lines were treated with Trastuzumab, Pertuzumab, and Lapatinib alone using different combinations and concentrations. Moreover, epidermal growth factor (EGF) or heregulin (HRG) was added to reveal potential growth factor-mediated compensatory effects. Receptor and intracellular signaling were analyzed as a function of cell treatment. Read-out parameters were cell proliferation and apoptosis. BT474 cells were efficiently driven into quiescence by Trastuzumab, but not by Pertuzumab treatment. Simultaneous EGF or HRG administration, however, restored the BT474 cell proliferation capacity. In contrast, neither therapeutic antibody treatment caused a profound inhibition of SK-BR-3 cell-cycle progress. Lapatinib turned out to be the most potent cell-cycle inhibitor in both cell lines even though its impact was significantly abrogated in the presence of EGF and HRG. The compensatory effect of EGF on Lapatinib-induced cell-cycle inhibition was reversed by Trastuzumab as well as by Pertuzumab treatment. Most importantly, HRGcaused compensation of Lapatinib-induced cell-cycle exit was reversed by Pertuzumab but not by Trastuzumab. Apparently, multiple anti-EGFR/Her2 targeting by using Trastuzumab, Pertuzumab, and Lapatinib more efficiently affects receptor function (interaction and activation) and consequently enhances their antiproliferative capacity. Growth inhibition by anticancer drugs targeted to Her/ErbB receptors, however, can be significantly undermined in the presence of EGF and in particular by HRG treatment, which suggests that specific therapeutic growth factor sequestration might further enhance anti-EGFR/Her2 targeting. '

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Section: Hrg-caused Compensation Of Lapatinib Treatment Is Efficientlmentioning

confidence: 93%

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confidence: 99%

Modular anti‐EGFR and anti‐Her2 targeting of SK‐BR‐3 and BT474 breast cancer cell lines in the presence of ErbB receptor‐specific growth factors

et al. 2011

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“…Pertuzumab, a humanized monoclonal antibody, is the first in a new class of HER2 dimerization inhibitors that block HER2 dimerization with other HER family members, thus inhibiting the downstream signaling processes that are associated with tumor growth and progression (26)(27)(28). Trastuzumab and pertuzumab bind to distinct epitopes on the HER2 extracellular domain, and it has been hypothesized that a combination of the two agents might provide a more effective inhibition of tumor growth than either agent alone (27,29).…”

Section: Introductionmentioning

confidence: 99%

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

et al. 2009

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The human epidermal growth factor receptor (HER) family plays an important role in cell survival and proliferation, and is implicated in oncogenesis. Overexpression of HER2 is associated with aggressive disease and poor prognosis. Trastuzumab is a humanized monoclonal antibody targeting HER2 and has proven survival benefit for women with HER2-positive early and metastatic breast cancer. Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with other HER family members such as HER3 and HER1. We investigated the antitumor activity of these agents alone and in combination in HER2-positive breast and non-small cell lung cancer xenografts. Our data show that the combination of trastuzumab and pertuzumab has a strongly enhanced antitumor effect and induces tumor regression in both xenograft models, something that cannot be achieved by either monotherapy. The enhanced efficacy of the combination was also observed after tumor progression during trastuzumab monotherapy. Near-IR fluorescence imaging experiments confirm that pertuzumab binding to tumors is not impaired by trastuzumab pretreatment. Furthermore, we show by in vitro assay that both trastuzumab and pertuzumab potently activate antibody-dependent cellular cytotoxicity. However, our data suggest that the strongly enhanced antitumor activity is mainly due to the differing but complementary mechanisms of action of trastuzumab and pertuzumab, namely inhibition of HER2 dimerization and prevention of p95HER2 formation. [Cancer Res 2009;69(24):9330-6]

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“…However, although breast cancer is one of the most intensely studied human tumors, the genetic analyses of chromosomal alterations and gene mutations have not established the critical sequence of events that lead to the development of sporadic breast cancer (Wijdan, 2009;Pickl andRies, 2009 andDiermeier-Daucher et al, 2008). It is possible that genetic heterogeneity may have obscured the basis for sporadic breast cancer and may explain, at least in part, why the genetic alterations are still not understood completely.…”

Section: Introductionmentioning

confidence: 99%

Early Diagnosis of Breast Cancer using Molecular, Biochemical and Pathological Markers

El-Assal¹

2011

American Journal of Applied Sciences

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Problem statement: Laboratory diagnosis of breast cancer in most of the hospitals has traditionally been performed using cell culture and the direct hormone receptor assay, which are money and time consuming. Approach: This study was performed in order to direct the attention toward increasing the efficiency of early diagnosis in clinical laboratories at the western region of KSA and Egypt using recent PCR-dependent protocols i.e., Randomly Amplified Polymorphic DNA (RAPD's) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Expression of HER4 oncogene using RT-PCR and immunohistochemical (IHC) staining have been assessed as early diagnostic for breast cancer. RT-PCR has detected HER4 expression in 52% of Invasive Duct breast Cancer (IDC) and this expression was significantly correlated with HER4 gene expression by IHC. Also we have selected sixteen 10-mer RAPD primers that have shown high percentage of identity to exons of different human oncogenes, such as V-myc, HER2, HER4, BRCA1 and BRCA2. Results: Only 13 out of the selected RAPD primers have revealed 19 distinguishable polymorphic markers between patient and normal females. Moreover, analysis of total protein profile identified extra markers and some differences at the level of Low Molecular Weight (LMW) protein among the two classes of females. Conclusion: These data will provide molecular, biochemical and pathological markers that can be used in KSA and Egypt clinical laboratories as additional efficient tools for early diagnosis of breast cancer.

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Flow Cytometric FRET Analysis of erbB Receptor Interaction on a Cell‐by‐Cell Basis

Cited by 18 publications

References 28 publications

Modular anti‐EGFR and anti‐Her2 targeting of SK‐BR‐3 and BT474 breast cancer cell lines in the presence of ErbB receptor‐specific growth factors

Modular anti‐EGFR and anti‐Her2 targeting of SK‐BR‐3 and BT474 breast cancer cell lines in the presence of ErbB receptor‐specific growth factors

Strongly Enhanced Antitumor Activity of Trastuzumab and Pertuzumab Combination Treatment on HER2-Positive Human Xenograft Tumor Models

Early Diagnosis of Breast Cancer using Molecular, Biochemical and Pathological Markers

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