ErbB Tyrosine Kinases and the Two Neuregulin Families Constitute a Ligand-Receptor Network

Pinkas‐Kramarski, Ronit; Shelly, Maya; Guarino, Bradley C.; Wang, Ling Mei; Lyass, Ljuba; Alroy, Iris; Alimandi, Maurizio; Kuo, Angera H.; Moyer, James D.; Lavi, Sara; Eisenstein, Miriam; Ratzkin, Barry; Seger, Rony; Bacus, Sarah; Pierce, Jacalyn H.; Andrews, Glenn C.; Yarden, Yosef

doi:10.1128/mcb.19.12.8695

Cited by 27 publications

(48 citation statements)

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“…Like neuregulin-1, also neuregulin-2, -3 and -4 were described to stimulate cell proliferation, provided the cells express the appropriate receptors [21,23,220,221]. Moreover, suggesting a similar dual function as has been described for neuregulin-1, also neuregulin-2 can induce differentiation of breast cancer cells in vitro, the strength and biochemical characteristics of the effect depending on the isoform applied [222][223][224]. The only report on expression of neuregulins-2, -3 or -4 in cancer is an immunohistochemical study of breast cancers using home-made polyclonal antibodies to each of the neuregulin family members [225].…”

Section: Regulation Of Hrg Expressionmentioning

confidence: 92%

Roles for neuregulins in human cancer

Stove

Bracke

2005

Clin Exp Metastasis

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The human epidermal growth factor (EGF) receptor (HER) family of receptor tyrosine kinases has frequently been implicated in cancer. Apart from overexpression or mutation of these receptors, also the aberrant autocrine or paracrine activation of HERs by EGF-like ligands may be important in cancer progression. Neuregulins constitute a family of EGF-like ligands that bind to HER3 or HER4, preferably forming heterodimers with the orphan receptor HER2. Mesenchymal neuregulin typically serves as a pro-survival and pro-differentiation signal for adjacent epithelia. Disruption of the balance between proliferation and differentiation, because of autocrine production by the epithelial cells, increased sensitivity to paracrine signals or disruption of the spatial organization, may lead to constitutive receptor activation, in the absence of receptor overexpression. Consequently, the analysis of ligand expression and/or activated receptors in tumor samples may broaden the group of patients that can benefit from targeted therapies.

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Section: Regulation Of Hrg Expressionmentioning

confidence: 92%

Roles for neuregulins in human cancer

Stove

Bracke

2005

Clin Exp Metastasis

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“…As described for HRG-1, HRG2 proteins are also involved in the induction of cell proliferation as well as in the control of cell differentiation, depending on the expression of the appropriate receptors and the HRG-2 isoforms present [57][58][59]. Furthermore, HRG-2 has been proposed to inhibit angiogenesis on the basis of its ability to inhibit proliferation of endothelial cells [60].…”

Section: Structure Of Hrgmentioning

confidence: 97%

“…Thus, signaling by ErbB2-containing receptor dimers is relatively prolonged and results in enhanced activation of signaling pathways. Indeed, ErbB2-ErbB3, which seems to be the most potent heterodimer, was shown to be highly mitogenic [57,111]. HRG proteins are the only ligands capable of activating all four ErbB receptors by heterodimerization, which allows a broader range of biological effects induced by these ligands.…”

Section: Hrg Acts As a Ligand For The Erbb3 And Erbb4 Receptorsmentioning

confidence: 98%

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Role of heregulin in human cancer

Breuleux

2007

Cell. Mol. Life Sci.

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Heregulin (HRG) is a soluble secreted growth factor, which, upon binding and activation of ErbB3 and ErbB4 transmembrane receptor tyrosine kinases, is involved in cell proliferation, invasion, survival and differentiation of normal and malignant tissues. The HRG gene family consists of four members: HRG-1, HRG-2, HRG-3 and HRG-4, of which a multitude of different isoforms are synthesized by alternative exon splicing, showing various tissue distribution and biological activities. Disruption of the physiological balance between HRG ligands and their ErbB receptors is implicated in the formation of a variety of human cancers. The general mechanisms involved in HRG-induced tumorigenesis is discussed.

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“…As a consequence, overexpression of HER-2 is indicative of poor clinical outcome of breast cancer patients. In addition to HER-2 (EGFR-2), EGFR-1 and associated downstream signaling pathways involved in the control of cell proliferation have been recognized as potential therapeutic targets in cancer and other disorders [94].…”

Section: Agents Targeting Growth Factor Signaling Cascadesmentioning

confidence: 99%

New Molecular Targets of Breast Cancer Therapy

Sauer

Deissler²,

Kurzeder³

2002

Strahlenther Onkol

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Typical dose escalation studies leading to the highest clinically still tolerated dose do not appear to be equally appropriate for the estimation of efficiency of those compounds as for conventional cytotoxic regimes. Rather, escalation up to an amount of therapeutic agent that is sufficient for maximum target inhibition should be promoted, where classical measures of cytoreduction such as complete or partial remission are replaced both by time to progression and treatment failure as an appropriate measure of the efficacy of an agent.

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ErbB Tyrosine Kinases and the Two Neuregulin Families Constitute a Ligand-Receptor Network

Abstract: The two isoforms of neuregulin 2 (NRG2), NRG2-␣ and NRG2-␤, were accidentally mislabeled. The names should therefore be exchanged throughout the paper, except in Fig. 9.

Cited by 27 publications

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Roles for neuregulins in human cancer

Roles for neuregulins in human cancer

Role of heregulin in human cancer

New Molecular Targets of Breast Cancer Therapy

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