title: ΔNp63α mediates proliferation and apoptosis in human gastric cancer cells by the regulation of GATA-6.
abstract: The oncogenic isoform of the p63 protein, ΔNp63α, has been found to be overexpressed in numerous human squamous cell carcinomas. However, the role of ΔNp63α in human gastric cancer remains unknown. To evaluate this role, we screened a panel of gastric cancer cell lines for ΔNp63α expression and found that they are correlated with the differentiation status of the cell lines. Using the MKN28 gastric cancer cell line for loss-of-function or gain-of-function of ΔNp63α in our experiments, we observed that forced expression of ΔNp63α promoted cell proliferation as assessed by the MTT and colony formation assays, and increased the GATA-6 expression. In contrast, down-regulation of ΔNp63α via small interfering RNA suppressed cell proliferation, induced cell apoptosis, and reduced the expression of GATA-6. In conclusion, our data suggest that ΔNp63α plays an important role in cell growth and proliferation of gastric cancer cells, which may be associated with the regulation of GATA-6 expression. This is the first study exploring the biological functions and the underlying mechanism of ΔNp63α during gastric cancer development. It also identifies potential targets for anti-tumor treatment.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050992:GATA5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050991:GATA4 Transcription Factor; D050992:GATA5 Transcription Factor; D050993:GATA6 Transcription Factor; D034741:RNA, Small Interfering; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA