Abstract
Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2 sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells to apoptosis induction through genotoxic stress imposed by sub-lethal concentration of hydrogen peroxide. Together, our findings suggest a potential autocrine pathway of p53 activation by transcriptional regulation, and a new approach to reactivate p53 for cancer therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / physiology*
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Apoptosis
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Base Sequence
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Cell Adhesion Molecules
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Cell Line, Tumor
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Cell Proliferation
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Cellular Senescence / physiology*
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DNA Primers
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Humans
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology*
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Male
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Neoplasm Proteins / physiology*
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Transcriptional Activation / physiology*
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Tumor Suppressor Protein p53 / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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Cell Adhesion Molecules
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DNA Primers
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Neoplasm Proteins
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PDZD2 protein, human
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Tumor Suppressor Protein p53