Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model

Danielsson, Frida (författare): KTH,Science for Life Laboratory, SciLifeLab,HPR/M UHLÉN

Skogs, Marie (författare): KTH,Proteomik,Science for Life Laboratory, SciLifeLab

Huss, Mikael (författare): Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)

Rexhepaj, Elton (författare): KTH,Science for Life Laboratory, SciLifeLab,HPR/M UHLÉN

O'Hurley, Gillian (författare): Uppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab

Klevebring, Daniel (författare): Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab

Pontén, Fredrik (författare): Uppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab

Uhlén, Mathias (författare): KTH,Proteomik,Science for Life Laboratory, SciLifeLab

Lundberg, Emma (författare): KTH,Proteomik,Science for Life Laboratory, SciLifeLab

(creator_code:org_t)

2013-04-08
2013
Engelska.
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:17, s. 6853-6858

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Abstract Ämnesord

Stäng

The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that similar to 6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.

NATURVETENSKAP -- Biologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences (hsv//eng)
NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Av författaren/redakt...: Danielsson, Frid ...; Skogs, Marie; Huss, Mikael; Rexhepaj, Elton; O'Hurley, Gillia ...; Klevebring, Dani ...; visa fler...; Pontén, Fredrik; Gad, Annica K. B ...; Uhlén, Mathias; Lundberg, Emma; visa färre...

Om ämnet

Av lärosätet: Kungliga Tekniska Högskolan; Karolinska Institutet; Stockholms universitet; Uppsala universitet

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