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Protein 4.1B suppresses prostate cancer progression and metastasis

ABSTRACT: Protein 4.1B is a 4.1/ezrin/radixin/moesin (FERM) domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers and breast carcinomas. However, its potential tumor suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Downregulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. As expression of Protein 4.1B is frequently downregulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease. Keywords: disease state

ORGANISM(S): Homo sapiens

PROVIDER: GSE7930 | GEO | 2007/07/02

SECONDARY ACCESSION(S): PRJNA100091

REPOSITORIES: GEO

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Transcription profiling of human prostate cancer primary cell line vs metastasis cell line reveals Protein 4.1B suppresses prostate cancer progression and metastasis

Project description:Protein 4.1B is a 4.1/ezrin/radixin/moesin (FERM) domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers and breast carcinomas. However, its potential tumor suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Downregulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. As expression of Protein 4.1B is frequently downregulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease. Experiment Overall Design: primary cell line vs metastasis cell line

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