C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

Travis, A; Pinder, S; Robertson, John F.R.; Bell, Jane M.; Wencyk, P.M.; Gullick, William J.; Nicholson, R. I.; Poller, David; Blamey, R. W.; Elston, C.W.; Ellis, Ian O.

doi:10.1038/bjc.1996.342

Cited by 117 publications

(104 citation statements)

References 20 publications

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“…For example, Sanidas et al demonstrated that the c-erbB-3 protein was always expressed in both gastric carcinoma and the adjacent mucosa, but the expression level was usually higher in the carcinoma (Sanidas et al, 1993). Travis et al observed that breast carcinoma expressed c-erbB-3 more intensely and diffusely than the adjacent normal glands which were usually weakly or moderately positive for this protein (Travis et al, 1996). Haugen et al showed that normal follicles of the thyroid were all negative for c-erbB-3, whereas all types of thyroid carcinoma expressed this protein with very high incidence (Haugen et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Thus far, of the four receptors, the expression of EGF-R and c-erbB-2 has been investigated in various neoplasms, including malignancies of the liver and biliary tract (Brunt and Swanson, 1992;Collier et al, 1992;Nakapoulou et al, 1994;Lee and Pirdas, 1995;Kira et al, 1997;Terada et al, 1998). The other two receptors, c-erbB-3 and c-erbB-4, have only been studied in depth for a few neoplasms (Sanidas et al, 1993;Simpson et al, 1995;Shintani et al, 1995;Haugen et al, 1996;Travis et al, 1996;Bobrow et al, 1997;Bodey et al, 1997;Chow et al, 1997;Ibrahim et al, 1997;Srinivasan et al, 1998Srinivasan et al, , 2000Suo et al, 1998;Freiss et al, 1999;Haussler et al, 1999;Kapitanovic et al, 2000;Kew et al, 2000), and little is known about their expression in hepatic malignancies. In this study, we investigated the expression of all four components of this family in a large series of HCC to evaluate their clinical significance and to identify the factors reflecting the development of this carcinoma.…”

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confidence: 99%

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Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Ito

Takeda

Sakon³

et al. 2001

Br J Cancer

269

204

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In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Ito

Takeda

Sakon³

et al. 2001

Br J Cancer

269

204

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“…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%

“…194 Two studies concluded reduced survival associated with ERBB3 protein overexpression, 195,201 whereas several other investigations did not. 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.…”

Section: Erbb3 In Normal and Neoplastic Tissues Cell Transformation Bmentioning

confidence: 99%

“…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: 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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Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells

Egeblad

Jäättelä

2000

Int. J. Cancer

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The ErbB receptor tyrosine kinase family consists of the epidermal growth factor (EGF) receptor (ErbB1) and three related receptors (ErbB2, ErbB3, ErbB4). Their intrinsic tyrosine kinases can be activated by receptor‐dimerization induced by numerous ligands or overexpression. ErbB receptors are frequently overexpressed in breast cancer, and their overexpression is associated with protection from apoptosis. To directly assess their role in apoptosis sensitivity of breast cancer cells, we established MCF‐7 breast carcinoma cell lines overexpressing each ErbB receptor alone or in all possible pairs. Overexpression of ErbB1, ErbB2 and ErbB4 receptors was enough to activate them as judged by their phosphorylation, whereas co‐expression of other ErbB receptors was necessary for the phosphorylation of the ErbB3. Surprisingly, overexpression of the ErbB receptors even when combined with treatment with their ligands (EGF, transforming growth factor α, betacellulin, neuregulins) failed to protect the MCF‐7 cells from cell death induced by either tumor necrosis factor (TNF) or serum starvation. During starvation TGF‐α, however, increased the cell size of the ErbB1 overexpressing cell line, and neuregulin1‐β1 increased that of all cell lines. In conclusion, our data does not support the role of ErbB receptors in the regulation of cell death induced by TNF or serum starvation, and the observed association in breast cancer may be due to other concomitant changes. Int. J. Cancer 86:617–625, 2000. © 2000 Wiley‐Liss, Inc.

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C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

Cited by 117 publications

References 20 publications

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

The ERBB3 receptor in cancer and cancer gene therapy

Cell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells

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