Regulation, Function, and Tissue-Specific Expression of Cytochrome P450 CYP1B1

Abstract

Cytochrome P450 CYP1B1 is a relatively recently identified member of the CYP1 gene family. The purpose of this commentary is to review the regulatory mechanisms, metabolic specificity, and tissue-specific expression of this cytochrome P450 and to highlight its unique properties. The regulation of CYP1B1 involves a variety of both transcriptional and post-transcriptional mechanisms. CYP1B1 can metabolize a range of toxic and carcinogenic chemicals in vitro but in some cases with a unique stereoselectivity. Estradiol 4-hydroxylation appears to be a characteristic reaction catalyzed by human CYP1B1. However, there are considerable species differences regarding the regulation, metabolic specificity, and tissue-specific expression of this P450. In humans CYP1B1 is overexpressed in tumor cells, and this has important implications for tumor development and progression and the development of anticancer drugs specifically activated by CYP1B1.

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

“…This gene might serve as an early transformation marker in oral epithelium in agreement with its postulated role as a tumor marker in other epithelial tissues. 32 Overall, the results indicate that NOK and SVpgC2a cultures can serve as valuable tools in studies of cancer development. The results now presented should clearly be followed by future assessment of protein levels and activity measurements to confirm the translation of the mRNAs into functional enzymes.…”

“…Interestingly, high CYP1A1, CYP1B1 and AHR expression likely reflect co-expression of enzymes in a metabolic pathway since the AHR is known to control induction of these CYPs. 32,33 Increased CYP1B1 expression has been reported in various carcinomas and other tumors although without assessment of oral epithelium. 32,34,35 Long-term culture in serum-free EMHA may serve to induce the AHR receptor pathway in oral keratinocytes, or alternatively, the noted changes in SVpgC2a might reflect its transformed phenotype.…”

“…32,33 Increased CYP1B1 expression has been reported in various carcinomas and other tumors although without assessment of oral epithelium. 32,34,35 Long-term culture in serum-free EMHA may serve to induce the AHR receptor pathway in oral keratinocytes, or alternatively, the noted changes in SVpgC2a might reflect its transformed phenotype. Indeed, the results in SVpgC2a indicate that expression of CYP1B1 may increase at an early stage of malignant transformation.…”

Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention

“…Before the identification of CYP1B1 as a novel metabolic enzyme, it has been detected in mouse endometrial stromal cells as a polycyclic aromatic hydrocarbon -inducible CYP (2) and was subsequently characterized (3). Since then, much interest has been placed on the inducibility of CYP1B1, especially given that it is differentially expressed within the tumor microenvironment of several human cancers (4)(5)(6). Although CYP1B1 is expressed in normal tissues (6,7), it is expressed at much higher levels in tumor cells compared with the surrounding normal tissue (4,5).…”

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

“…In addition, CYP1B1 metabolizes 17β-estradiol to form a catechol metabolite that cause DNA damage (Han and Liehr, 1994). It has been demonstrated that the expression level of CYP1B1 protein is higher in various types of cancer compared with normal tissue (Murray et al, 1997), whereas there is no difference in the CYP1B1 mRNA levels between cancerous and normal tissues (Cheung et al, 1999) implying post-transcriptional regulation. This background prompted us to investigate the possibility that human CYP1B1 might be regulated by miRNA, and we found that it is negatively regulated by miR-27b via translational repression (Tsuchiya et al, 2006).…”