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Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG, Catchpoole D, Deery MJ, Malik K - Mol Oncol (2014)

Bottom Line: Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining.PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells.Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epigenetics Laboratory University of Bristol, Bristol BS8 1TD, UK.

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Related in: MedlinePlus

For PRMT5 immunohistochemistry controls, we used skeletal muscle which is negative for PRMT5 (left) and normal prostate where PRMT5 expression has been reported to be strong in the nucleus of the epithelial cells (Gu et al., 2012) (right). Weak staining in the blood vessels is indicated (ves), contrasting with the skeletal muscle (ske). Note the strong nuclear staining in prostate epithelial cells (epi) contrasting with the myoepithelium (myo).
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undfig4: For PRMT5 immunohistochemistry controls, we used skeletal muscle which is negative for PRMT5 (left) and normal prostate where PRMT5 expression has been reported to be strong in the nucleus of the epithelial cells (Gu et al., 2012) (right). Weak staining in the blood vessels is indicated (ves), contrasting with the skeletal muscle (ske). Note the strong nuclear staining in prostate epithelial cells (epi) contrasting with the myoepithelium (myo).


Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG, Catchpoole D, Deery MJ, Malik K - Mol Oncol (2014)

For PRMT5 immunohistochemistry controls, we used skeletal muscle which is negative for PRMT5 (left) and normal prostate where PRMT5 expression has been reported to be strong in the nucleus of the epithelial cells (Gu et al., 2012) (right). Weak staining in the blood vessels is indicated (ves), contrasting with the skeletal muscle (ske). Note the strong nuclear staining in prostate epithelial cells (epi) contrasting with the myoepithelium (myo).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359099&req=5

undfig4: For PRMT5 immunohistochemistry controls, we used skeletal muscle which is negative for PRMT5 (left) and normal prostate where PRMT5 expression has been reported to be strong in the nucleus of the epithelial cells (Gu et al., 2012) (right). Weak staining in the blood vessels is indicated (ves), contrasting with the skeletal muscle (ske). Note the strong nuclear staining in prostate epithelial cells (epi) contrasting with the myoepithelium (myo).
Bottom Line: Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining.PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells.Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epigenetics Laboratory University of Bristol, Bristol BS8 1TD, UK.

Show MeSH
Related in: MedlinePlus