The HSD17B11 Knockout NCI-H1975 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population targeting the HSD17B11 gene in the NCI-H1975 human lung adenocarcinoma epithelial cell line. This polyclonal population contains a heterogeneous mix of cells with disruptions in the HSD17B11 locus, enabling functional studies of gene loss without clonal selection biases. The CRISPR/Cas9-mediated gene disruption serves as a robust model for investigating HSD17B11-dependent cellular processes.
The NCI-H1975 cell line is derived from a nonsmoking female with lung adenocarcinoma and harbors activating EGFR L858R/T790M and PIK3CA mutations, making it a well-established model for studying tyrosine kinase inhibitor resistance and downstream signaling in non-small cell lung cancer. These cells retain epithelial characteristics and are widely employed to dissect the metabolic and signaling adaptations that drive tumor progression and therapeutic evasion.
HSD17B11 encodes a short-chain dehydrogenase/reductase that localizes to the endoplasmic reticulum and lipid droplets, where it catalyzes the oxidation/reduction of 17??-hydroxysteroids and retinoids. Its expression is transcriptionally regulated by PPAR??, LXR??, and SREBP1. At the lipid droplet surface, HSD17B11 directly interacts with perilipin-2 (ADRP) and perilipin-3 (TIP47), and its function is dependent on retinol-binding protein 1 (CRBP1). Through these interactions, the enzyme controls the interconversion of active and inactive androgens, estrogens, and retinoids, thereby modulating steroid hormone homeostasis and the generation of retinoic acid. Consequently, HSD17B11 acts upstream of retinoic acid receptor (RAR) and retinoid X receptor (RXR) signaling and influences the expression of lipid droplet structural proteins PLIN2 and PLIN3.
In the context of NCI-H1975 cells, disrupting HSD17B11 perturbs lipid droplet biogenesis and retinoic acid metabolism, which may intersect with oncogenic EGFR and PIK3CA pathways. Loss of HSD17B11 function is expected to alter cellular lipid storage, steroidogenic output, and retinoic acid-mediated transcriptional programs, providing a unique tool to dissect the crosstalk between oncogenic signaling and metabolic homeostasis. This model is particularly relevant for exploring how lipid droplet dynamics and retinoic acid signaling contribute to tumor cell proliferation, differentiation, and drug sensitivity.
Researchers can utilize these polyclonal knockout cells to investigate lung adenocarcinoma metabolism, steroid hormone signaling, lipid droplet biology, and mechanisms of drug resistance. Representative assays include Western blotting and RT-qPCR for expression analysis, BODIPY staining of lipid droplets, cell proliferation and apoptosis assays, RARE luciferase reporters for retinoic acid signaling, steroid mass spectrometry, and EGFR inhibitor sensitivity tests. This product is intended for advanced biomedical research and is available exclusively through Ascent Research.
