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A mechanistic role for the chromatin modulator, NAP1L1, in pancreatic neuroendocrine neoplasm proliferation and metastases.

ABSTRACT:

Background

The chromatin remodeler NAP1L1, which is upregulated in small intestinal neuroendocrine neoplasms (NENs), has been implicated in cell cycle progression. As p57(Kip2) (CDKN1C), a negative regulator of proliferation and a tumor suppressor, is controlled by members of the NAP1 family, we tested the hypothesis that NAP1L1 may have a mechanistic role in regulating pancreatic NEN proliferation through regulation of p57(Kip2).

Results

NAP1L1 silencing (siRNA and shRNA/lipofectamine approach) decreased proliferation through inhibition of mechanistic (mammalian) target of rapamycin pathway proteins and their phosphorylation (p?ConclusionNAP1L1 is over-expressed in pancreatic neuroendocrine neoplasm metastases and epigenetically promotes cell proliferation through regulation of p57 (Kip2) promoter methylation.

SUBMITTER: Schimmack S

PROVIDER: S-EPMC4112619 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A mechanistic role for the chromatin modulator, NAP1L1, in pancreatic neuroendocrine neoplasm proliferation and metastases.

Schimmack Simon S Taylor Andrew A Lawrence Ben B Alaimo Daniele D Schmitz-Winnenthal Hubertus H Büchler Markus W MW Modlin Irvin M IM Kidd Mark M

Epigenetics & chromatin 20140721

<h4>Background</h4>The chromatin remodeler NAP1L1, which is upregulated in small intestinal neuroendocrine neoplasms (NENs), has been implicated in cell cycle progression. As p57(Kip2) (CDKN1C), a negative regulator of proliferation and a tumor suppressor, is controlled by members of the NAP1 family, we tested the hypothesis that NAP1L1 may have a mechanistic role in regulating pancreatic NEN proliferation through regulation of p57(Kip2).<h4>Results</h4>NAP1L1 silencing (siRNA and shRNA/lipofect ...[more]

PMID: 25071868

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