The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells.

Abstract

NSD3/WHSC1L1 histone methyltransferase gene aberrations are observed in leukemia and in breast and lung carcinomas, suggesting that NSD3 is implicated in carcinogenesis. In this study we examined in human breast cancer cells the NSD3L isoform which contains the catalytic histone methyltransferase SET-domain. siRNA directed depletion of NSD3L followed by genome-wide microarray analysis identified NSD3L regulated genes which could be functionally linked to cellular signaling pathways such as cell growth, cell cycle, cell motility, transcription, and apoptosis. Notably up-regulated genes are the cell cycle regulators E2F2 and Arl2. In accordance with a function of NSD3L in cell cycle regulation NSD3L depletion resulted in an increase in the number of cells in the S and G2/M cell cycle phases. Moreover, NSD3L depletion increased the invasiveness of MDA-MB-231 breast cancer cells indicating that NSD3L normally restrain cellular metastatic potential. Together the presented data indicates that NSD3L is a candidate tumor suppressor.

• Authors: Zhangle Zhou, Rune Thomsen, Søren Kahns, Anders Lade Nielsen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 398 Issue 3 Pg. 565-70 (Jul 30 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20599755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Nuclear Proteins
• Protein Isoforms
• RNA, Small Interfering
• Tumor Suppressor Proteins
• Histone-Lysine N-Methyltransferase
• NSD3 protein, human

Topics

• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Genome-Wide Association Study
• Histone-Lysine N-Methyltransferase (genetics, metabolism)
• Humans
• Neoplasm Invasiveness
• Nuclear Proteins (genetics, metabolism)
• Protein Isoforms (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Tumor Suppressor Proteins (genetics, metabolism)