Epidermal‐growth‐factor‐receptor expression is associated with rapid tumor proliferation in bladder cancer

Sauter, Guido; Haley, John D.; Chew, Karen; Kerschmann, Russell; Moore, Dan H.; Carroll, Peter R.; Moch, Holger; Gudat, F; Mihatsch, Michael J.; Waldman, Frederic M.

doi:10.1002/ijc.2910570412

Cited by 94 publications

(84 citation statements)

References 17 publications

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“…HER1 expression has been reported by a number of groups to be an informative prognostic indicator for TCC (17)(18)(19)(20). Increased HER1 expression has also been linked spatially to local increases in cell proliferation (21), suggesting a role for one or more HER1 ligands in aberrant urothelial cell growth. However, several reports have shown that EGF does not promote the growth of normal human urothelial cells (HUC) in serum-free medium, despite the presence of high-affinity EGF binding sites in these cells (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

Freeman¹,

et al. 1997

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The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases. ( J. Clin. Invest. 1997. 99:1028-1036.)

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Section: Introductionmentioning

confidence: 99%

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

Freeman¹,

et al. 1997

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“…Increased numbers of EG F R s are often found in bladder carcinoma and the over expression has proven closely related to tumour stage and malignancy grade (10)(11)(12)(13). U nfortunately, for targeted therapy, the EG F Rs are distributed among various normal tissues as well as tumours (14,15).…”

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confidence: 99%

HER-2 - A Possible Target for Therapy of Metastatic Urinary Bladder Carcinoma

et al. 2002

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“…3,4,8,[14][15][16] The expression of EGFR in glioblastoma, lung and bladder cancer is often associated with polysomy or amplification of EGFR. 4,17 Some studies suggested that the expression of EGFR and/or an increased EGFR copy number could be associated with responsiveness to erlotinib. 17 Our study confirmed data by Thomas et al 18 showing that EGFR overexpression in synovial sarcoma cannot be linked to an increase in EGFR gene copy number.…”

Section: Discussionmentioning

confidence: 99%

“…In some tumor types, EGFR expression is associated with poor clinical outcome. 3,4 In synovial sarcoma, the immunohistochemical detection of the EGFR protein has been first described in 1985. 5 Subsequent investigations demonstrated that EGFR expression is more frequently found in synovial sarcomas than in other soft tissue tumors.…”

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confidence: 99%

Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma

et al. 2006

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The prognosis of patients with synovial sarcomas is poor. New therapeutic strategies, such as target inhibition of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) with erlotinib and gefinitib, could be effective, because most synovial sarcomas overexpress this protein. In lung cancer, the responsiveness to gefinitib is strongly related to the presence of mutations in the tyrosine kinase domain of the EGFR gene, while erlotinib sensitivity seems to be partly linked to chromosome 7 polysomy or gene amplification. To clarify the role of EGFR in synovial sarcoma and to explore the potential for a targeted therapy approach, we have examined 13 of these soft tissue tumors. We have analyzed the EGFR expression by immunohistochemistry, searched for polysomy and gene amplification with fluorescence in situ hybridization (FISH) and screened for EGFR mutations in exons 18-21 using PCR and direct sequencing. All 13 tumors showed strong diffuse or focal EGFR expression. No amplifications of the EGFR gene were found. In contrast, several point mutations were identified in exons 18-21 of two synovial sarcomas. Whereas one of these tumors carried only a synonymous mutation, two missense mutations in exons 19 and 21 of the EGFR gene (P733S and A840 T, respectively) could be demonstrated in the second sample. In conclusion, strong EGFR expression in synovial sarcomas is not related to gene amplification. The existence of mutations in the tyrosine kinase domain of the EGFR gene in a small subset of synovial sarcomas suggests that only few patients may profit from the tyrosine kinase inhibitor therapy.

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Epidermal‐growth‐factor‐receptor expression is associated with rapid tumor proliferation in bladder cancer

Cited by 94 publications

References 17 publications

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

HER-2 - A Possible Target for Therapy of Metastatic Urinary Bladder Carcinoma

Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma

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