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Author, Editor(s)

Author(s):

Schulz, Wolfgang A.
Alexa, Adrian
Jung, Volker
Hader, Christiane
Hoffmann, Michele J.
Yamanaka, Masanori
Fritzsche, Sandy
Wlazlinski, Agnes
Müller, Mirko
Lengauer, Thomas
Engers, Rainer
Florl, Andrea R.
Wullich, Bernd
Rahnenführer, Jörg

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Not MPG Author(s):

Schulz, Wolfgang A.
Jung, Volker
Hader, Christiane
Hoffmann, Michele J.
Yamanaka, Masanori
Fritzsche, Sandy
Wlazlinski, Agnes
Müller, Mirko
Engers, Rainer
Florl, Andrea R.
Wullich, Bernd

BibTeX cite key*:

Rahnenfuehrer2007c

Title

Title*:

Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer


Rahnenfuehrer2007c.pdf (763 KB)

Journal

Journal Title*:

Molecular Cancer

Journal's URL:


Download URL
for the article:

http://dx.doi.org/10.1186/1476-4598-6-14

Language:

English

Publisher

Publisher's
Name:


Publisher's URL:


Publisher's
Address:


ISSN:


Vol, No, pp, Date

Volume*:

6

Number:


Publishing Date:

2007

Pages*:

1-16

Number of
VG Pages:


Page Start:

14.1

Page End:

14.16

Sequence Number:

14

DOI:

10.1186/1476-4598-6-14

Note, Abstract, ©

Note:


(LaTeX) Abstract:

Background

Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their relationship in less advanced prostate cancers.

Results

In 50 primary tumor tissues, no correlation was observed between chromosome 8 alterations determined by comparative genomic hybridization and LINE-1 hypomethylation measured by Southern blot hybridization. The discrepancy towards the former study, which had been dominated by advanced stage cases, suggests that both alterations converge and interact during prostate cancer progression. Therefore, interaction analysis was performed on microarray-based expression profiles of cancers harboring both alterations, only one, or none. Application of a novel bioinformatic method identified Gene Ontology (GO) groups related to innate immunity, cytoskeletal organization and cell adhesion as common targets of both alterations. Many genes targeted by their interaction were involved in type I and II interferon signaling and several were functionally related to hereditary prostate cancer genes. In addition, the interaction appeared to influence a switch in the expression pattern of EPB41L genes encoding 4.1 cytoskeleton proteins. Real-time RT-PCR revealed GADD45A, MX1, EPB41L3/DAL1, and FBLN1 as generally downregulated in prostate cancer, whereas HOXB13 and EPB41L4B were upregulated. TLR3 was downregulated in a subset of the cases and associated with recurrence. Downregulation of EPB41L3, but not of GADD45A, was associated with promoter hypermethylation, which was detected in 79% of carcinoma samples.

Conclusion

Alterations of chromosome 8 and DNA hypomethylation in prostate cancer probably do not cause each other, but converge during progression. The present analysis implicates their interaction in innate immune response suppression and cytoskeletal changes during prostate cancer progression. The study thus highlights novel mechanisms in prostate cancer progression and identifies novel candidate genes for diagnostic and therapeutic purposes. In particular, TLR3 expression might be useful for prostate cancer prognosis and EPB41L3 hypermethylation for its detection.


URL for the Abstract:

http://www.molecular-cancer.com/content/6/1/14

Categories,
Keywords:


HyperLinks / References / URLs:


Copyright Message:

© 2007 Schulz et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Personal Comments:


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Access Level:

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Correlation

MPG Unit:

Max-Planck-Institut für Informatik



MPG Subunit:

Computational Biology and Applied Algorithmics

Appearance:

MPII WWW Server, MPII FTP Server, MPG publications list, university publications list, working group publication list, Fachbeirat, VG Wort


BibTeX Entry:

@ARTICLE{Rahnenfuehrer2007c,
AUTHOR = {Schulz, Wolfgang A. and Alexa, Adrian and Jung, Volker and Hader, Christiane and Hoffmann, Michele J. and Yamanaka, Masanori and Fritzsche, Sandy and Wlazlinski, Agnes and M{\"u}ller, Mirko and Lengauer, Thomas and Engers, Rainer and Florl, Andrea R. and Wullich, Bernd and Rahnenf{\"u}hrer, J{\"o}rg},
TITLE = {Factor interaction analysis for chromosome 8 and {DNA} methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer},
JOURNAL = {Molecular Cancer},
YEAR = {2007},
VOLUME = {6},
PAGES = {1--16},
DOI = {10.1186/1476-4598-6-14},
}


Entry last modified by Ruth Schneppen-Christmann, 03/24/2009
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Editor(s)
Jörg Rahnenführer
Created
02/15/2007 09:58:14 AM
Revisions
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Editor(s)
Ruth Schneppen-Christmann
Ruth Schneppen-Christmann
Ruth Schneppen-Christmann
Ruth Schneppen-Christmann
Ruth Schneppen-Christmann
Edit Dates
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24.03.2009 09:22:24
24.03.2009 09:07:53
24.03.2009 09:07:35
19.03.2009 13:48:04
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