Quinlan Kate G R, Verger Alexis, Yaswen Paul, Crossley Merlin
School of Molecular and Microbial Biosciences, G08, University of Sydney, NSW 2006, Australia.
Biochim Biophys Acta. 2007 Jun;1775(2):333-40. doi: 10.1016/j.bbcan.2007.05.001. Epub 2007 May 22.
Chromosome 20q13 is highly amplified in human cancers, including 20-30% of early stage human breast cancers. The amplification correlates with poor prognosis. Over-expression of the zinc-finger protein 217 (ZNF217), a candidate oncogene on 20q13.2, in cultured human mammary and ovarian epithelial cells can lead to their immortalization, indicating that selection for ZNF217 expression may drive 20q13 amplification during critical early stages of cancer progression. ZNF217 can also attenuate apoptotic signals resulting from exposure to doxorubicin, suggesting that ZNF217 expression may also be involved in resistance to chemotherapy. Recent findings indicate that ZNF217 binds specific DNA sequences, recruits the co-repressor C-terminal binding protein (CtBP), and represses the transcription of a variety of genes. Inappropriate expression of ZNF217 may lead to aberrant down-regulation of genes involved in limiting the proliferation, survival, and/or invasiveness of cancer cells. Better understanding of ZNF217 and its associated pathways may provide new targets for therapeutic intervention in human cancers.
20号染色体长臂13区在人类癌症中高度扩增，包括20% - 30%的早期人类乳腺癌。这种扩增与预后不良相关。位于20号染色体长臂13.2区的候选癌基因锌指蛋白217（ZNF217）在培养的人乳腺和卵巢上皮细胞中过表达可导致细胞永生化，这表明在癌症进展的关键早期阶段，对ZNF217表达的选择可能驱动20号染色体长臂13区的扩增。ZNF217还可减弱因接触阿霉素而产生的凋亡信号，提示ZNF217表达可能也参与化疗耐药。最近的研究结果表明，ZNF217结合特定的DNA序列，招募共抑制因子C末端结合蛋白（CtBP），并抑制多种基因的转录。ZNF217的异常表达可能导致参与限制癌细胞增殖、存活和/或侵袭的基因异常下调。更好地了解ZNF217及其相关通路可能为人类癌症的治疗干预提供新的靶点。
