Memorial Sloan-Kettering Cancer Center, Program in Molecular Pharmacology and Experimental Therapeutics, 1275 York Avenue, New York, NY, 10021, U.S.A.,
Cytotechnology. 1998 Sep;27(1-3):257-69. doi: 10.1023/A:1008032716628.
The emergence of resistance in a tumor population is most often associated with a disregulation of gene expression, usually at the level of transcription. A major goal in the field of cancer chemotherapy is to define the mechanisms underlying transcriptional regulation of drug resistance genes in an effort to identify targets for therapeutic intervention. Recently, considerable progress has been made in identifying the molecular mechanisms involved in the transcriptional regulation of the P-glycoprotein (Pgp) gene. When overexpressed in tumor cells, Pgp confers resistance to a variety of chemotherapeutic agents; this resistance has been termed MDR (multidrug resistance). Moreover, Pgp is a normal component of a variety of highly differentiated cell types and, as such, is regulated by both internal and external environmental stimuli. In this review, we will discuss the current knowledge regarding the DNA elements and protein factors involved in both constitutive and inducible regulation of Pgp transcription in normal and tumor cells.
肿瘤群体中耐药性的出现通常与基因表达失调有关，通常是在转录水平上。癌症化疗领域的一个主要目标是确定药物耐药基因转录调控的机制，以确定治疗干预的靶点。最近，在鉴定参与 P 糖蛋白 (Pgp) 基因转录调控的分子机制方面取得了相当大的进展。当在肿瘤细胞中过度表达时，Pgp 赋予对多种化疗药物的耐药性；这种耐药性被称为 MDR（多药耐药性）。此外，Pgp 是多种高度分化细胞类型的正常组成部分，因此受内部和外部环境刺激的调节。在这篇综述中，我们将讨论关于正常和肿瘤细胞中 Pgp 转录的组成性和诱导性调节涉及的 DNA 元件和蛋白因子的最新知识。
