Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes.

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Research Abstract Details 

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Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Abstract Text:

Kuo Ping Chiu,Pramila Ariyaratne,Han Xu,Adrian Tan,Patrick Ng,Edison Tak-Bun Liu,Yijun Ruan,Chia-Lin Wei,Wing-Kin Ken Sung,

BACKGROUND: Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET) approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. METHODS: GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo). Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. RESULTS: Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain region(s) of the pathway. Expression levels of c-Myc and Trp53 were also higher in melanoma. Moreover, transcriptional variants resulted from alternative transcription start sites or alternative polyadenylation sites were found in Ras and genes encoding adhesion or cytoskeleton proteins such as integrin, beta-catenin, alpha-catenin, and actin. CONCLUSION: The highly correlated results unmistakably point to a systematic downregulation of mitochondrial activities, which we hypothesize aims to downgrade the mitochondria-mediated apoptosis and the dependency of cancer cells on angiogenesis. Our results also demonstrate the advantage of using the PET approach in conjunction with KEGG database for systematic pathway analysis.

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Publishing Authors By Initials

KP Chiu,P Ariyaratne,H Xu,A Tan,P Ng,ET Liu,Y Ruan,CL Wei,WK Sung,

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: BMC cancer

VOLUME: 7

Page Numbers: 109

Journal Abbreviation: BMC Cancer

ISSN: 1471-2407

DAY: 26

MONTH: 06

YEAR: 2007

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Information

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LANGUAGE: eng

NlmUniqueID: 100967800

Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: pathology

Chemical & Substance for Abstract: Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes. Information

Substance Name: RNA, Messenger

Registry Number: 0

Grant and Affiliation Information for Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes.

AFFILIATION: Genome Institute of Singapore, Genome #02-01, Singapore. chiukp@gis.a-star.edu.sg

Country: England

AGENCY: United States NHGRI

GRANT: 1R01HG003521-01

ACRONYM: HG

MEDLINETA: BMC Cancer

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