Laboratory of Molecular Pathology of Cancer, Faculty of Health Sciences, University of Brasília, Brasília, DF 70.910-900, Brazil.
Int J Oncol. 2013 Aug;43(2):653-60. doi: 10.3892/ijo.2013.1981. Epub 2013 Jun 10.
The histone lysine methyltransferases contain a SET domain, which catalyzes the addition of methyl groups to specific lysine residues. The MLL family of genes encodes histone-modifying enzymes with histone 3-lysine 4 methyltransferase activity that can regulate gene transcription. The MLL family exists in multi-protein complexes and has been implicated in a variety of processes including normal development and cell growth. Although some of the MLL family members have already been described to be involved in cancer, a clear relationship of these genes with breast cancer is not determined to date. In the present study, we used quantitative PCR to investigate the expression profile of all five MLL genes [MLL (ALL-1), MLL2, MLL3, MLL4 and MLL5] in 7 breast cancer cell lines, 8 breast tumors and adjacent non-tumor tissues and in 12 normal tissues. We observed a diminished expression of all five genes in the breast cancer cell lines when compared to normal breast tissue. We found a significantly decreased expression of MLL2 in the tumor samples compared to the non-tumor controls. In tumor samples, MLL5 also showed a clear suppression tendency. Among the normal tissues analyzed, all genes showed a markedly higher expression in skeletal muscle and brain. Although further studies are required to determine the exact role of these methyltransferases in cancer development, our results indicate that the suppression of MLL genes, especially MLL2 and 5, take part in modulating breast carcinogenesis. Our assessment of the MLL family gene expression patterns in a diverse set of breast cancer cell lines and in a multitude of tissue types and breast tumors should lead to increasingly detailed information on the involvement of these genes in cancer progression.
组蛋白赖氨酸甲基转移酶包含一个 SET 结构域，该结构域催化将甲基基团添加到特定的赖氨酸残基上。MLL 家族的基因编码具有组蛋白 3-赖氨酸 4 甲基转移酶活性的组蛋白修饰酶，可调节基因转录。MLL 家族存在于多蛋白复合物中，并与多种过程有关，包括正常发育和细胞生长。尽管已经描述了一些 MLL 家族成员参与癌症，但这些基因与乳腺癌的确切关系尚未确定。在本研究中，我们使用定量 PCR 研究了 7 种乳腺癌细胞系、8 种乳腺癌肿瘤和相邻非肿瘤组织以及 12 种正常组织中所有 5 个 MLL 基因（MLL（ALL-1）、MLL2、MLL3、MLL4 和 MLL5）的表达谱。与正常乳腺组织相比，我们观察到乳腺癌细胞系中所有 5 个基因的表达均降低。与非肿瘤对照相比，我们发现肿瘤样本中 MLL2 的表达明显降低。在肿瘤样本中，MLL5 也表现出明显的抑制趋势。在分析的正常组织中，所有基因在骨骼肌和大脑中的表达明显更高。尽管还需要进一步研究来确定这些甲基转移酶在癌症发展中的确切作用，但我们的结果表明，MLL 基因的抑制，特别是 MLL2 和 5，参与调节乳腺癌发生。我们对不同乳腺癌细胞系和多种组织类型和乳腺癌肿瘤中 MLL 家族基因表达模式的评估，应导致对这些基因在癌症进展中的参与的信息越来越详细。
