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Apoptosis 2008 Aug;13(8):993-1004

Molecular mechanism underlying differential apoptosis between human melanoma cell lines UACC903 and UACC903(+6) revealed by mitochondria-focused cDNA microarrays.

Zhang Q, Wu J, Nguyen A, Wang BD, He P, Laurent GS, Rennert OM, Su YA

Su, YA, George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Room 555,2300 I St NW, Washington, DC 20037 USA George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA Univ Antioquia, Immunovirol Biogenesis Grp, Medellin, Colombia; NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA

Abstract

Human malignant melanoma cell line UACC903 is resistant to apoptosis while chromosome 6-mediated suppressed cell line UACC903(+6) is sensitive. Here, we describe identification of differential molecular pathways underlying this difference. Using our recently developed mitochondria-focused cDNA microarrays, we identified 154 differentially expressed genes including proapoptotic (BAK1 [6p21.3], BCAP31, BNIP1, CASP3, CASP6, FAS, FDX1, FDXR, TNFSF10 and VDAC1) and antiapoptotic (BCL2L1, CLN3 and MCL1) genes. Expression of these pro- and anti-apoptotic genes was higher in UACC903(+6) than in UACC903 before UV treatment and was altered after UV treatment. qRT-PCR and Western blots validated microarray results. Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines.


Category: Journal Article
PubMed ID: #18563568
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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