Aberrant activation of notch signaling in human breast cancer
A role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. However, it...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2006-02, Vol.66 (3), p.1517-1525 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | STYLIANOU, Spyros CLARKE, Rob B BRENNAN, Keith |
| description | A role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease. |
| doi_str_mv | 10.1158/0008-5472.CAN-05-3054 |
| format | Article |
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However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. 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However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease.</description><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Receptor, Notch1 - antagonists & inhibitors</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Receptors, Notch - metabolism</subject><subject>Signal Transduction</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMtOwzAQRS0EoqXwCSBvYJdix48kCxZVxUuqYANra-LarVHiFDtF4u9x1IiuRnd07ox0ELqmZE6pKO8JIWUmeJHPl4u3jIiMEcFP0JQKVmYF5-IUTf-ZCbqI8StFQYk4RxMquchzUk7Rw6I2IYDvMeje_UDvOo87i33X6y2ObuOhcX6DncfbfQse18FA7LEGr024RGcWmmiuxjlDn0-PH8uXbPX-_LpcrDItCtpnxuaWS2CMV7LmuRVU5yBrqct12vLCsqq2hFOp84oZyzU11ALodV1RSW3OZujucHcXuu-9ib1qXdSmacCbbh8VLbisJJMJFAdQhy7GYKzaBddC-FWUqMGbGpyowYlK3hQRavCWejfjg33dmvWxNYpKwO0IQNTQ2KRMu3jkigQKJtgfXUB1mw</recordid><startdate>20060201</startdate><enddate>20060201</enddate><creator>STYLIANOU, Spyros</creator><creator>CLARKE, Rob B</creator><creator>BRENNAN, Keith</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope></search><sort><creationdate>20060201</creationdate><title>Aberrant activation of notch signaling in human breast cancer</title><author>STYLIANOU, Spyros ; CLARKE, Rob B ; BRENNAN, Keith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c571t-ef2f46a33496b42f51c2a6b6c8d6a347f39bf0416c293ef4c1e1faacdb9161f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Receptor, Notch1 - antagonists & inhibitors</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Receptors, Notch - metabolism</topic><topic>Signal Transduction</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STYLIANOU, Spyros</creatorcontrib><creatorcontrib>CLARKE, Rob B</creatorcontrib><creatorcontrib>BRENNAN, Keith</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STYLIANOU, Spyros</au><au>CLARKE, Rob B</au><au>BRENNAN, Keith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant activation of notch signaling in human breast cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>66</volume><issue>3</issue><spage>1517</spage><epage>1525</epage><pages>1517-1525</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>A role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. 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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Apoptosis - physiology Biological and medical sciences Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cell Transformation, Neoplastic - metabolism Epithelial Cells - metabolism Epithelial Cells - pathology Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical sciences Receptor, Notch1 - antagonists & inhibitors Receptor, Notch1 - metabolism Receptors, Notch - metabolism Signal Transduction Tumors |
| title | Aberrant activation of notch signaling in human breast cancer |
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