Dataset Information

?Np63? enhances the oncogenic phenotype of osteosarcoma cells by inducing the expression of GLI2.

ABSTRACT:

Background

?Np63, a splice variant of p63, is overexpressed and exhibits oncogenic activity in many cancers including pancreatic and breast cancer and promotes cell survival by inhibiting apoptosis. Despite its role in tumorigenesis, mechanistic activity of ?Np63 mediated oncogenic function in osteosarcoma is poorly understood.

Methods

The expression levels of p63 isoforms in osteosarcoma cell lines were identified using quantitative techniques. Expression profiling using microarray, siRNA mediated loss-of-function, and chromatin immunoprecipitation assays were employed to identify novel ?Np63? targets in p63-null osteosarcoma SaOS-2 cells that were engineered to express ?Np63?. The phenotype of SaOS-2-?Np63? cells was assessed using wound-healing, colony formation, and proliferation assays.

Results

The comparative expression analyses identified ?Np63? as the predominant p63 isoform expressed by invasive OS cell lines. Phenotypic analyses of SaOS-2-?Np63? cells in vitro indicate that ?Np63? imparted tumorigenic attributes upon tumor cells. Further, we show that in osteosarcoma cells ?Np63? directly regulated the transcription factor GLI2, which is a component of the hedgehog signaling pathway, and that functional interactions between ?Np63? and GLI2 confer oncogenic properties upon OS cells.

Conclusions

Here, we report that GLI2 is the novel target gene of ?Np63? and that ?Np63?-GLI2 crosstalk in osteosarcoma cells is a necessary event in osteosarcoma progression. Defining the exact mechanisms involved in this interaction that mediate the pathogenesis of osteosarcoma promises to identify targets for drug therapy.

SUBMITTER: Ram Kumar RM

PROVIDER: S-EPMC4125704 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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ΔNp63α enhances the oncogenic phenotype of osteosarcoma cells by inducing the expression of GLI2.

Ram Kumar Ram Mohan RM Betz Michael M MM Robl Bernhard B Born Walter W Fuchs Bruno B

BMC cancer 20140801

<h4>Background</h4>ΔNp63, a splice variant of p63, is overexpressed and exhibits oncogenic activity in many cancers including pancreatic and breast cancer and promotes cell survival by inhibiting apoptosis. Despite its role in tumorigenesis, mechanistic activity of ΔNp63 mediated oncogenic function in osteosarcoma is poorly understood.<h4>Methods</h4>The expression levels of p63 isoforms in osteosarcoma cell lines were identified using quantitative techniques. Expression profiling using microarr ...[more]

PMID: 25085524

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