Molecular Mechanism Underlying Differential Apoptosis Between Human Melanoma Cell Lines UACC903 and UACC903(+6) Revealed by Mitochondria-focused CDNA Microarrays

Overview

Journal Apoptosis

Publisher Springer

Date 2008 Jun 20

PMID 18563568

Citations 10

Authors

Qiuyang Zhang

Jun Wu

Anhthu Nguyen

Bi-Dar Wang

Ping He

Georges St Laurent

Owen M Rennert

Yan A Su

Affiliations

Soon will be listed here.

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.

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