| Spinophilin: a new tumor suppressor at 17q21. | |
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MedLine Citation:
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PMID: 22515982 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The scaffold protein spinophilin (SPN) is a regulatory subunit of phosphatase 1a (PP1a) located at 17q21.33. This region is frequently associated with microsatellite instability and LOH and contains a relatively high density of known tumor suppressor genes, and several unidentified candidate tumor suppressor genes located distal to BRCA1. Spn is located in this locus and proposed to be a new tumor suppressor. Loss of Spn induces a proliferative response by increasing pRb phosphorylation, which in turn activates p53, thereby, neutralizing the proliferative response. The absence of p53 bypasses this barrier and enhances the malignant phenotype. Furthermore, the ectopic expression of SPN in human tumor cells from different types of malignancies greatly reduced cell growth. Spn knock-out mice had decreased lifespan with increased cellular proliferation in tissues such as the mammary ducts and early appearance of tumors. Furthermore, the combined loss of Spn and mutant p53 activity led to increased mammary carcinomas, confirming the functional relationship between p53 and Spn. In human tumors, Spn is absent in 20% and reduced in another 37% of human lung tumors. Spn reduction correlates with malignant grade and p53 mutations. Furthermore, Spn mRNA is lost in a percentage of renal carcinomas and lung adenocarcinomas. Finally, lower levels of Spn mRNA correlate with higher grade of ovarian carcinoma and chronic myelogenous leukemia. Therefore, Spn may be the tumor suppressor gene that is located at 17q21.33 and that its tumor suppressive function is dependent on the absence of p53. |
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Authors:
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Amancio Carnero |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-18 |
Journal Detail:
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Title: Current molecular medicine Volume: - ISSN: 1875-5666 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101093076 Medline TA: Curr Mol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Instituto de Biomedicina de Sevilla, Consejo Superior de Investigaciones Cientificas, Avda. Manuel Siurot s/n. 41013, Sevilla, Spain. acarnero@us.es. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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