c‐<i>erb</i>B‐3 protein expression in human breast cancer: comparison with other tumour variables and survival

Quinn, Cecily; Ostrowski, J.L.; Lane, Sally; Loney, D.P.; Teasdale, J.; Benson, E. A.

doi:10.1111/j.1365-2559.1994.tb01324.x

Cited by 70 publications

(57 citation statements)

References 16 publications

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“…This suggests that expression of HER1 and HER2 is involved in tumour progression and poor prognosis in the bladder tumours only when HER3 and HER4 are low. In keeping with our results, studies on breast cancer investigating the expression of the individual EGF receptors also show that increased HER3 and HER4 expression appears to be associated with better prognosis (Quinn et al, 1994;Knowlden et al, 1998). However, it should be noted that in another study, only HER4 was found to be associated with a better prognosis whereas HER1, HER2 and HER3 overexpression was associated with a poor outcome (Witton et al, 2003).…”

Section: Discussionsupporting

confidence: 89%

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

et al. 2006

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Increased expression of the epidermal growth factor (EGF) receptors, HER1 and HER2 are related to poor prognosis in most cancers studied. Recently, a high expression of the two remaining receptors of the EGF system, HER3 and HER4 has been related to a favourable prognosis. However, prognostic significance of HER1 and HER2 receptors in bladder cancer is controversial and the effect of the expression of different combinations of these receptors on patient survival is not well understood. Therefore, we examined the mRNA expression of all four EGF receptors with real-time polymerase chain reaction in biopsies from 88 patients with bladder cancer, where the survival was followed for a median of 38.5 months (range 1 -117 months). Expression of HER1 and HER2 alone showed no correlation with survival. However, a high expression of HER1 together with high expression of HER3 and HER4 correlated to a better prognosis compared to the high expression of HER1 together with low expression of HER3 and HER4 (P ¼ 0.0006). Also, a significantly longer survival was observed in patients expressing high HER2 when coexpressed with high HER3 and HER4, as compared to the survival in patients with tumours expressing high HER2 but low HER3 and HER4 (P ¼ 0.0005). Our results suggest that the final outcome of patients with high HER1-and HER2-expressing tumours depends on the expression of HER3 and HER4.

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Section: Discussionsupporting

confidence: 89%

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

et al. 2006

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“…Overexpression of ErbB-3 has been demonstrated in breast cancer and its expression demonstrated in multiple myeloma. [38][39][40] The expression of these proteins is significant in that they suggest the activity of other important signaling pathways in the pathogenesis of HL.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive identification of proteins in Hodgkin lymphoma-derived Reed–Sternberg cells by LC-MS/MS

Wallentine

Kim

Seiler

et al. 2007

Laboratory Investigation

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Mass spectrometry-based proteomics in conjunction with liquid chromatography and bioinformatics analysis provides a highly sensitive and high-throughput approach for the identification of proteins. Hodgkin lymphoma is a form of malignant lymphoma characterized by the proliferation of Reed-Sternberg cells and background reactive lymphocytes. Comprehensive analysis of proteins expressed and released by Reed-Sternberg cells would assist in the discovery of potential biomarkers and improve our understanding of its pathogenesis. The subcellular proteome of the three cellular compartments from L428 and KMH2 Hodgkin lymphoma-derived cell lines were fractionated, and analyzed by reversephase liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Additionally, proteins released by Hodgkin lymphoma-derived L428 cells were extracted from serum-free culture media and analyzed. Peptide spectra were analyzed using TurboSEQUEST s against the UniProt protein database (5.26.05; 188 712 entries). A subset of the identified proteins was validated by Western blot analysis, immunofluorescence microscopy and immunohistochemistry. A total of 1945 proteins were identified with 785 from the cytosolic fraction, 305 from the membrane fraction, 441 from the nuclear fraction and 414 released proteins using a minimum of two peptide identifications per protein and an error rate of o5.0%. Identification of proteins from diverse functional groups reflected the functional complexity of the Reed-Sternberg proteome. Proteins with previously reported oncogenic function in other cancers and from signaling pathways implicated in Hodgkin lymphoma were identified. Selected proteins without previously demonstrated expression in Hodgkin lymphoma were validated by Western blot analysis (B-RAF, Erb-B3), immunofluorescence microscopy (Axin1, Tenascin-X, Mucin-2) and immunohistochemistry using a tissue microarray (BRAF, PIM1). This study represents the first comprehensive inventory of proteins expressed by Reed-Sternberg cells of Hodgkin lymphoma and demonstrates the utility of combining cellular subfractionation, protein precipitation, tandem mass spectrometry and bioinformatics analysis for comprehensive identification of proteins that may represent potential biomarkers of the disease.

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“…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%

“…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. 186 In another study, ERBB3 mRNA had twofold higher expression on average compared with isolated mammary epithelial cells, but there was considerable variability and lack of statistical significance.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

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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c‐erbB‐3 protein expression in human breast cancer: comparison with other tumour variables and survival

Cited by 70 publications

References 16 publications

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients

Comprehensive identification of proteins in Hodgkin lymphoma-derived Reed–Sternberg cells by LC-MS/MS

The ERBB3 receptor in cancer and cancer gene therapy

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