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摘要
<jats:p>Pancreatic neuroendocrine tumors (PanNET) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of PanNET. It has been shown that the <jats:styled-content style="fixed-case">mTOR</jats:styled-content> inhibitor everolimus can improve the progression‐free survival of PanNET patients, suggesting that inhibition of the <jats:styled-content style="fixed-case">PI</jats:styled-content>3K‐Akt‐<jats:styled-content style="fixed-case">mTOR</jats:styled-content> pathway may suppress the progression of Pan<jats:styled-content style="fixed-case">NET</jats:styled-content>. <jats:styled-content style="fixed-case">PHLDA</jats:styled-content>3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to <jats:styled-content style="fixed-case">PIP</jats:styled-content><jats:sub>3</jats:sub>. Our analysis of Pan<jats:styled-content style="fixed-case">NET</jats:styled-content> revealed frequent loss‐of‐heterozygosity and <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation at the <jats:italic><jats:styled-content style="fixed-case">PHLDA</jats:styled-content>3</jats:italic> locus, resulting in strong suppression of <jats:italic><jats:styled-content style="fixed-case">PHLDA</jats:styled-content>3</jats:italic> transcription. Such alterations in the <jats:italic><jats:styled-content style="fixed-case">PHLDA</jats:styled-content>3</jats:italic> gene were also frequently found in lung neuroendocrine tumors (NET), suggesting the possibility that various types of <jats:styled-content style="fixed-case">NET</jats:styled-content> have in common the functional loss of the <jats:italic><jats:styled-content style="fixed-case">PHLDA</jats:styled-content>3</jats:italic> gene.</jats:p>
- 出版日期2017-6
