Application of RNA-Seq transcriptome analysis: CD151 is an Invasion/Migration target in all stages of epithelial ovarian cancer

Journal of Ovarian Research

John A Martignetti⁴  Peter Dottino³  Ravi Sachidanandam⁴  Maurizio D'Incalci²  Sergio Marchini¹  Robert Fruscio⁵  Samantha Cohen³  Peter Schlosshauer⁶  Fei Huang⁴  Hardik Shah⁴  Emir Senturk⁴  Li Lin⁴  Rebecca A Mosig⁴ 

[1] Department of Oncology, Instituto "Mario Negri", Milano, Italy;Mario Negri Gynecological Oncology Group (MaNGO), Milano, Italy;Division of Gynecologic Oncology, Mount Sinai School of Medicine, New York, NY, USA;Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA;San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy;Department of Pathology, Mount Sinai School of Medicine, New York, NY, USA

关键词: RNA-Seq;    Metastasis;    Migration;    Invasion;    Epithelial Ovarian Cancer;    CD151;   

Others  :  815192
DOI  :  10.1186/1757-2215-5-4

 received in 2011-11-21, accepted in 2012-01-24,  发布年份 2012

【 摘 要 】

Background

RNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status of a tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC).

Methods

Specifically, we sought candidate invasion/migration targets based on expression levels across all tumors, novelty of expression in EOC, and known function. RNA-Seq analysis revealed the high expression of CD151, a transmembrane protein, across all stages of EOC. Expression was confirmed at both the mRNA and protein levels using RT-PCR and immunohistochemical staining, respectively.

Results

In both EOC tumors and normal ovarian surface epithelial cells we demonstrated CD151 to be localized to the membrane and cell-cell junctions in patient-derived and established EOC cell lines. We next evaluated its role in EOC dissemination using two ovarian cancer-derived cell lines with differential levels of CD151 expression. Targeted antibody-mediated and siRNA inhibition or loss of CD151 in SKOV3 and OVCAR5 cell lines effectively inhibited their migration and invasion.

Conclusion

Taken together, these findings provide the first proof-of-principle demonstration for a next generation sequencing approach to identifying candidate therapeutic targets and reveal CD151 to play a role in EOC dissemination.

【 授权许可】

   
2012 Mosig et al; licensee BioMed Central Ltd.

【 图 表 】

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