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Visit our Expo - Redox and Inflammation signaling 2012

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Session X : Cell death in cancer Poster X, 80<br />

Over-expression of microRNA-21 modulates phosphoinositide-3 kinase <strong>and</strong> PTEN<br />

<strong>signaling</strong> <strong>and</strong> promotes tumor cell survival.<br />

Tushar Patel, Fanyin Meng, Roger Henson, Hania Wehbe, Molly Lang<br />

Scott <strong>and</strong> White Clinic, Texas A&M University System Health Science Center College of<br />

Medicine, 2401 South 31st Street, Temple, TX 76508, U.S.A. E-mail:<br />

tpatel@swmail.sw.org<br />

MicroRNAs (miRNAs) are endogenous RNA molecules that can regulate gene expression.<br />

Altered expression of miRNA such as miR-21 has been reported for several different cancers.<br />

However the role of miR-21 in tumor progression <strong>and</strong> the mechanisms involved remain<br />

unknown. Our aims were to assess the effect of miR-21 on critical survival <strong>signaling</strong><br />

pathways. Methods: A miRNA microarray was used to profile the miRNA expression in<br />

malignant (KMCH, Mz-ChA-1 <strong>and</strong> TFK) <strong>and</strong> non-malignant (H69) cholangiocyte cell lines.<br />

Expression of miR-21 was confirmed by Northern blot <strong>and</strong> real-time PCR. miR-21<br />

expression was altered using mir-21 specific antisense oligonulceotides or mir-21 precursor<br />

miRNAs. Expression of PTEN <strong>and</strong> p85 was assessed by Western blots. For in vivo studies,<br />

homogenates were obtained from xenografts of Mz-ChA-1 cells in nude mice under basal<br />

conditions or following treatment with gemcitabine. Results: miR-21 expression was<br />

increased in all malignant cell lines compared to non-malignant H69 cholangiocytes (2.74 ±<br />

0.11 fold in Mz-ChA-1 cells, 4.35 ± 0.14 fold in TFK cells, <strong>and</strong> 1.84 ± 0.03 fold in KMCH-1<br />

cells; all p

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