The role of SPINK1 in ETS rearrangement-negative prostate cancers Journal Article
| Authors: | Tomlins, S. A.; Rhodes, D. R.; Yu, J.; Varambally, S.; Mehra, R.; Perner, S.; Demichelis, F.; Helgeson, B. E.; Laxman, B.; Morris, D. S.; Cao, Q.; Cao, X.; Andren, O.; Fall, K.; Johnson, L.; Wei, J. T.; Shah, R. B.; Al-Ahmadie, H.; Eastham, J. A.; Eggener, S. E.; Fine, S. W.; Hotakainen, K.; Stenman, U. H.; Tsodikov, A.; Gerald, W. L.; Lilja, H.; Reuter, V. E.; Kantoff, P. W.; Scardino, P. T.; Rubin, M. A.; Bjartell, A. S.; Chinnaiyan, A. M. |
| Article Title: | The role of SPINK1 in ETS rearrangement-negative prostate cancers |
| Abstract: | ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers (∼10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers. © 2008 Elsevier Inc. All rights reserved. |
| Keywords: | immunohistochemistry; human tissue; treatment outcome; human cell; dna-binding proteins; cancer recurrence; united states; reproducibility of results; gene; cohort studies; gene expression; gene expression profiling; tumor markers, biological; rna, small interfering; risk factors; recurrence; gene function; rna interference; cancer cell culture; cell line, tumor; transfection; risk assessment; transcription factors; prostate cancer; cancer invasion; europe; gleason score; prostatic neoplasms; gene expression regulation, neoplastic; gene rearrangement; rna, messenger; oligonucleotide array sequence analysis; prostatectomy; nucleotide sequence; carrier proteins; gene fusion; cellbio; tissue array analysis; neoplasm invasiveness; trans-activators; humdisease; proto-oncogene proteins c-ets; spink1 gene |
| Journal Title: | Cancer Cell |
| Volume: | 13 |
| Issue: | 6 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2008-06-10 |
| Start Page: | 519 |
| End Page: | 528 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2008.04.016 |
| PUBMED: | 18538735 |
| PROVIDER: | scopus |
| PMCID: | PMC2732022 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 51" - "Export Date: 17 November 2011" - "CODEN: CCAEC" - "Molecular Sequence Numbers: GENBANK: NM_003122;" - "Source: Scopus" |
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