HER3 Is a Determinant for Poor Prognosis in Melanoma
Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and m...
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| Published in | Clinical cancer research Vol. 14; no. 16; pp. 5188 - 5197 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Philadelphia, PA
American Association for Cancer Research
15.08.2008
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated
with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance
and function in primary melanoma and metastases remains largely elusive.
Experimental Design: HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases
relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration,
invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines.
Results: We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may
serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival.
Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro . In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion
of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.
Conclusion: Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention. |
|---|---|
| AbstractList | The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive.
HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines.
We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.
Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention. Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive. Experimental Design: HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines. Results: We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro . In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines. Conclusion: Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention. The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive.PURPOSEThe epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive.HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines.EXPERIMENTAL DESIGNHER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines.We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.RESULTSWe show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention.CONCLUSIONOur results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention. Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive. Experimental Design: HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines. Results: We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines. Conclusion: Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention. |
| Author | Reinhard Dummer Daniela Mihic-Probst Markus Reschke Edward Htun van der Horst Peter J. Wild Markus Hutterer Stefanie Meyer Pjotr Knyazev Axel Ullrich Holger Moch |
| Author_xml | – sequence: 1 givenname: Markus surname: Reschke fullname: Reschke, Markus – sequence: 2 givenname: Daniela surname: Mihic-Probst fullname: Mihic-Probst, Daniela – sequence: 3 givenname: Edward Htun surname: van der Horst fullname: van der Horst, Edward Htun – sequence: 4 givenname: Pjotr surname: Knyazev fullname: Knyazev, Pjotr – sequence: 5 givenname: Peter J. surname: Wild fullname: Wild, Peter J. – sequence: 6 givenname: Markus surname: Hutterer fullname: Hutterer, Markus – sequence: 7 givenname: Stefanie surname: Meyer fullname: Meyer, Stefanie – sequence: 8 givenname: Reinhard surname: Dummer fullname: Dummer, Reinhard – sequence: 9 givenname: Holger surname: Moch fullname: Moch, Holger – sequence: 10 givenname: Axel surname: Ullrich fullname: Ullrich, Axel |
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| Snippet | Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated
with poor prognosis in... Purpose: The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in... The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung,... |
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| SubjectTerms | Adult Aged Aged, 80 and over anti-HER3 monoclonal antibodies Antineoplastic agents Apoptosis - physiology Biological and medical sciences Biomarkers, Tumor - analysis Blotting, Western Cell Line, Tumor Cell Movement - physiology Cell Proliferation Dermatology Female HER3 Humans Immunohistochemistry Kaplan-Meier Estimate Male Medical sciences melanoma Melanoma - metabolism Melanoma - mortality Melanoma - pathology Middle Aged Pharmacology. Drug treatments PI3K-AKT signaling Prognosis receptor tyrosine kinases Receptor, ErbB-3 - biosynthesis Reverse Transcriptase Polymerase Chain Reaction RNA Interference Skin Neoplasms - metabolism Skin Neoplasms - mortality Skin Neoplasms - pathology Tissue Array Analysis Tumors of the skin and soft tissue. Premalignant lesions |
| Title | HER3 Is a Determinant for Poor Prognosis in Melanoma |
| URI | http://clincancerres.aacrjournals.org/content/14/16/5188.abstract https://www.ncbi.nlm.nih.gov/pubmed/18698037 https://www.proquest.com/docview/69416160 |
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