Wilms' tumor gene 1 regulates p63 and promotes cell proliferation in squamous cell carcinoma of the head and neck

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Li, XingruUmeå universitet,Klinisk kemi (author)

Wilms' tumor gene 1 regulates p63 and promotes cell proliferation in squamous cell carcinoma of the head and neck

Article/chapterEnglish2015

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2015-05-01
Springer Science and Business Media LLC,2015
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LIBRIS-ID:oai:DiVA.org:umu-103386
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103386URI
https://doi.org/10.1186/s12885-015-1356-0DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Background: Wilms' tumor gene 1 (WT1) can act as a suppressor or activator of tumourigenesis in different types of human malignancies. The role of WT1 in squamous cell carcinoma of the head and neck (SCCHN) is not clear. Overexpression of WT1 has been reported in SCCHN, suggesting a possible oncogenic role for WT1. In the present study we aimed at investigating the function of WT1 and its previously identified protein partners p63 and p53 in the SCCHN cell line FaDu. Methods: Silencing RNA (siRNA) technology was applied to knockdown of WT1, p63 and p53 in FaDu cells. Cell proliferation was detected using MTT assay. Chromatin immunoprecipitation (ChIP)/PCR analysis was performed to confirm the effect of WT1 on the p63 promoter. Protein co-immunoprecipitation (co-IP) was used to find protein interaction between WT1 and p53/p63. Microarray analysis was used to identify changes of gene expression in response to knockdown of either WT1 or p63. WT1 RNA level was detected using real-time quantitative PCR (RT-qPCR) in patients with SCCHN. Results: We found that WT1 and p63 promoted cell proliferation, while mutant p53 (R248L) possessed the ability to suppress cell proliferation. We reported a novel positive correlation between WT1 and p63 expression. Subsequently, p63 was identified as a WT1 target gene. Furthermore, expression of 18 genes involved in cell proliferation, cell cycle regulation and DNA replication was significantly altered by downregulation of WT1 and p63 expression. Several known WT1 and p63 target genes were affected by WT1 knockdown. Protein interaction was demonstrated between WT1 and p53 but not between WT1 and p63. Additionally, high WT1 mRNA levels were detected in SCCHN patient samples. Conclusions: Our findings suggest that WT1 and p63 act as oncogenes in SCCHN, affecting multiple genes involved in cancer cell growth.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
WT1
p63
p53
Cell proliferation
Squamous cell carcinoma of the head and neck (SCCHN)

Added entries (persons, corporate bodies, meetings, titles ...)

Ottosson, SofiaUmeå universitet,Klinisk kemi (author)
Wang, SihanUmeå universitet,Klinisk kemi(Swepub:umu)siwa0003 (author)
Jernberg, EmmaUmeå universitet,Patologi(Swepub:umu)emahog04 (author)
Boldrup, LindaUmeå universitet,Patologi(Swepub:umu)liabop98 (author)
Gu, XiaolianUmeå universitet,Patologi(Swepub:umu)xinguu04 (author)
Nylander, KarinUmeå universitet,Patologi(Swepub:umu)kaanyr77 (author)
Li, AihongUmeå universitet,Klinisk kemi(Swepub:umu)liai0001 (author)
Umeå universitetKlinisk kemi (creator_code:org_t)

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In:BMC Cancer: Springer Science and Business Media LLC151471-2407

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By the author/editor: Li, Xingru; Ottosson, Sofia; Wang, Sihan; Jernberg, Emma; Boldrup, Linda; Gu, Xiaolian; show more...; Nylander, Karin; Li, Aihong; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Articles in the publication: BMC Cancer

By the university: Umeå University

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