The tumor suppressor PTEN interacts with p53 in hereditary cancer (Review)

Nakanishi,Atsuko; Kitagishi,Yasuko; Ogura,Yasunori; Matsuda,Satoru

doi:10.3892/ijo.2014.2377

The tumor suppressor PTEN interacts with p53 in hereditary cancer (Review)

Authors:
- Atsuko Nakanishi
- Yasuko Kitagishi
- Yasunori Ogura
- Satoru Matsuda
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Affiliations: Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
Published online on: April 10, 2014 https://doi.org/10.3892/ijo.2014.2377
Pages: 1813-1819

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Abstract

Numerous hereditary syndromes caused by mutations in multiple tumor suppressor genes can cause cancers. Germline mutations in PTEN and p53 tumor suppressor cause Cowden syndrome and Li-Fraumeni syndrome, respectively. There exists some phenotypic overlap in these syndromes, and they are associated with high risks of breast cancer. The tumor suppressor protein PTEN is a dual-specificity phosphatase which has protein phosphatase activity and lipid phosphatase activity that antagonizes PI3K activity. Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream targets. PTEN gene is recognized as one of the most frequently mutated or mutated in many human cancers. Li-Fraumeni syndrome results from germline mutations of the tumor suppressor p53 gene encoding a transcriptional factor able to regulate cell cycle and apoptosis when DNA damage occurs. The p53 protein cooperates with PTEN and might be an essential blockage in development of mammary tumors. Many findings have demonstrated that PTEN as well as p53 plays a critical role in DNA damage response. This review summarizes the function of PTEN and p53 in carcinogenic cell signaling. In addition, we will discuss the role of PTEN signaling through its interaction with p53 and MDM2 pathways for the potential implications in hereditary cancer prevention and therapeutic intervention.

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