Expression of c-erbB3 protein in primary breast carcinomas

Naidu, Rakesh; Yadav, Man Mohan; Nair, Satheesh; Kutty, Methil Kannan

doi:10.1038/bjc.1998.689

Cited by 160 publications

(125 citation statements)

References 37 publications

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“…200 There seems to be particular confusion regarding relationships between ERBB3 expression and estrogen receptor (ER). At the level of proteins as determined by immunohistochemistry, ERBB3 and ER did not correlate, 193,200 and a high percentage of ER-negative tumors were strongly positive for ERBB3. 193 Another study seemed to be confirmatory, showing a weak inverse relationship between ERBB3 protein and ER.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 85%

“…At the level of proteins as determined by immunohistochemistry, ERBB3 and ER did not correlate, 193,200 and a high percentage of ER-negative tumors were strongly positive for ERBB3. 193 Another study seemed to be confirmatory, showing a weak inverse relationship between ERBB3 protein and ER. 195 In cultured mammary cancer cells, estrogen treatment suppressed ERBB3 transcription.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 85%

“…184 In what appears to be the only direct study of ERBB3 protein, 2D-PAGE analysis of four normal and four malignant breast cancer samples revealed the presence of ERBB3 only in the malignant tissue. 191 Immunohistochemical approaches find ERBB3 protein to be detectable in 50-70% of human breast cancers, [192][193][194] with higher expression of ERBB3 in human breast cancers vs normal tissues in 18-29% of cases. 184,192,195 ERBB3 mRNAs evaluated by real-time PCR showed a 100-fold variation, and increased expression relative to normal in 46% of breast cancers.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

“…However, in another investigation high ERBB3 mRNA expression correlated with poor survival. 186 With regard to correlation between mammary cancer prognosis and ERBB3 protein status, high expression as determined by immuno-histochemistry has shown positive associations with metastasis, 184 tumor size and local recurrence, 200 tumor grade 193 and tumor recurrence. 194 Two studies concluded reduced survival associated with ERBB3 protein overexpression, 195,201 whereas several other investigations did not.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

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The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 85%

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 85%

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

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The ERBB3 receptor in cancer and cancer gene therapy

2008

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“…In particular, an abundance of evidence reveals that its intimate signalling partner HER3 plays an important and necessary function in HER2-mediated tumorigenesis. HER3 is frequently overexpressed in breast cancers with EGFR or HER2 overexpression (Naidu et al, 1998). Tumours arising in mice due to the transgenic overexpression of Neu are also characterised by increased expression and phosphorylation of HER3 (Siegel et al, 1999).…”

Section: Mechanism Of Her2 Tumorigenesis: the Role Of Her3mentioning

confidence: 99%

Targeting HER proteins in cancer therapy and the role of the non-target HER3

2007

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Members of the human epidermal growth factor receptor (HER) family have been of considerable interest in the cancer arena due to their potential to induce tumorigenesis when their signalling functions are deregulated. The constitutive activation of these proteins is seen in a number of different common cancer subtypes, and in particular EGFR and HER2 have become highly pursued targets for anti-cancer drug development. Clinical studies in a number of different cancers known to be driven by EGFR or HER2 show mixed results, and further mechanistic understanding of drug sensitivity and resistance is needed to realise the full potential of this treatment modality. Signalling in trans is a key feature of HER family signalling, and the activation of the PI3K/Akt pathway, so critically important in tumorigenesis, is driven predominantly through phosphorylation in trans of the kinase inactive member HER3. An increasing body of evidence shows that HER3 plays a critical role in EGFR-and HER2-driven tumours. In particular, HER3 lies upstream of a critically important tumorigenic signalling pathway with extensive ability for feedback and cross-talk signalling, and targeting approaches that fail to account for this important trans-target of EGFR and HER2 can be undermined by its resiliency and resourcefulness. Since HER3 is kinase inactive, it is not a direct target of kinase inhibitors and not presently an easily drugable target. This review presents the current evidence highlighting the role of HER3 in tumorigenesis and its role in mediating resistance to inhibitors of EGFR and HER2.

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Receptor Tyrosine Kinases

Matthews¹,

Gerritsen²

2010

Targeting Protein Kinases for Cancer Therapy

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Expression of c-erbB3 protein in primary breast carcinomas

Cited by 160 publications

References 37 publications

The ERBB3 receptor in cancer and cancer gene therapy

The ERBB3 receptor in cancer and cancer gene therapy

Targeting HER proteins in cancer therapy and the role of the non-target HER3

Receptor Tyrosine Kinases

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