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2016 ; 5
(8
): e257
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Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine
tumors and promotes the neoplastic phenotype
#MMPMID27548814
Maggi EC
; Trillo-Tinoco J
; Struckhoff AP
; Vijayaraghavan J
; Del Valle L
; Crabtree JS
Oncogenesis
2016[Aug]; 5
(8
): e257
PMID27548814
show ga
Neuroendocrine tumors (NETs), which can have survival rates as low as 4%,
currently have limited therapeutic interventions available highlighting the dire
need for the identification of novel biological targets for use as new potential
drug targets. One such potential target is retinoblastoma-binding protein 2
(RBP2), an H3K4 demethylase whose overexpression has been linked to cancer
formation and metastasis in non-endocrine tumor types. We measured RBP2 mRNA and
protein levels in enteropancreatic NETs by measuring RBP2 in matched human normal
and NET tissue samples. Further, proliferation, migration, invasion and colony
formation assays were performed in the physiologically relevant NET cell lines
?lox5, H727 and QGP-1 to understand the role of RBP2 and its demethylase activity
on end points of tumorigenesis. Our data indicate a strong correlation between
RBP2 mRNA and protein expression in NET specimens. RBP2 was overexpressed
relative to tissue-matched normal controls in 80% of the human tumors measured.
In vitro studies showed RBP2 overexpression significantly increased
proliferation, migration, invasion and colony formation, whereas knockdown
significantly decreases the same parameters in a demethylase-independent manner.
The cell cycle inhibitors p21 and p57 decreased with RBP2 overexpression and
increased upon its depletion, suggesting a regulatory role for RBP2 in cellular
proliferation. Taken together, our results support the hypothesis that the
aberrant overexpression of RBP2 is a frequent contributing factor to tumor
formation and metastasis in enteropancreatic NETs.