The AKR1C2 Knockout HeLa Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the HeLa cervical adenocarcinoma cell line, designed to disrupt the AKR1C2 gene and serve as a loss-of-function model for steroid hormone metabolism and detoxification research. This product provides a heterogeneous pool of edited cells, capturing the breadth of CRISPR-mediated gene disruption without clonal selection, making it suitable for population-level studies of AKR1C2 function in human epithelial cancer biology.
The host HeLa cell line is an HPV18-positive cervical adenocarcinoma-derived epithelial model originally isolated from a 31-year-old African American woman in 1951. As one of the most extensively used human cell lines, HeLa provides a robust and well-characterized platform for studying gene function, cell signaling, and cancer biology, with particular relevance to hormone-responsive pathways and xenobiotic metabolism.
AKR1C2 encodes aldo-keto reductase family 1 member C2, a cytosolic enzyme that catalyzes the NADPH-dependent reduction of progesterone to 20??-hydroxyprogesterone and dihydrotestosterone to 3??-androstanediol, thereby inactivating these potent steroid hormones. It also metabolizes prostaglandin E2, attenuating inflammatory signaling. AKR1C2 expression is transcriptionally regulated by the androgen receptor (AR), progesterone receptor (PGR), and the stress-responsive transcription factors NFE2L2 (Nrf2) and aryl hydrocarbon receptor (AHR). Disruption of AKR1C2 is expected to enhance AR and PR signaling due to decreased hormone catabolism, while also altering prostaglandin E2-mediated pathways, ultimately impacting cell proliferation, differentiation, and apoptosis.
In the HeLa context, which expresses functional steroid hormone receptors and prostaglandin synthesis machinery, AKR1C2 knockout provides a clean model to dissect its role in modulating hormone-dependent and inflammatory responses. This is particularly relevant for understanding the molecular basis of cancers where AKR1C2 dysregulation is implicated, such as prostate, breast, and endometrial cancers, as well as conditions like endometriosis and polycystic ovary syndrome. The polyclonal nature allows assessment of gene disruption effects across a population, mirroring heterogeneous tumor cell responses.
Key research applications include investigating mechanisms of hormone-dependent cancer progression, steroid and prostaglandin metabolism, drug resistance, and chemical carcinogen detoxification. Representative assays compatible with this model include Western blotting and RT-qPCR for AKR1C2 expression validation, LC-MS-based metabolite profiling of progesterone and DHT conversion, AR/PR luciferase reporter assays for transcriptional activity, prostaglandin E2 ELISA, and functional assays such as proliferation (MTS/BrdU), migration/invasion, and flow cytometry. These polyclonal knockout cells are an essential tool for functional genomics, signaling pathway analysis, and drug discovery in reproductive and hormone-sensitive cancer research. For more information, contact Ascent Research.
