The HSD17B11 Knockout A-549 Polyclonal Cells represent a ready-to-use CRISPR/Cas9-edited polyclonal knockout cell population derived from the parental A-549 cell line. This product features targeted disruption of the HSD17B11 gene, which encodes hydroxysteroid 17-beta dehydrogenase 11. The polyclonal knockout pool preserves genetic heterogeneity, facilitating robust loss-of-function studies without clonal selection artifacts. Researchers can leverage this model to interrogate HSD17B11-dependent steroid metabolism and its role in lung adenocarcinoma biology.
The host A-549 cell line is an adherent human non-small cell lung cancer model with epithelial morphology, originally established from a 58-year-old male with lung adenocarcinoma. Widely used to study respiratory epithelium and therapeutic responses, these cells provide a physiologically relevant context for investigating steroid hormone dynamics in lung malignancies, particularly given emerging evidence of hormonal influences on cancer progression.
HSD17B11 catalyzes the NAD+-dependent oxidation of 17-beta-hydroxysteroids to 17-ketosteroids. The enzyme converts estradiol (E2) to the weaker estrogen estrone (E1) and transforms 5??-androstane-3??,17??-diol (3??-diol) to the more potent dihydrotestosterone (DHT). By modulating intracellular estrogen and androgen levels, HSD17B11 influences downstream estrogen receptor (ESR1) and androgen receptor (AR) signaling. Its expression is regulated by upstream factors including AR, sterol regulatory element-binding protein 1c (SREBP1c), and liver X receptor alpha (LXR??). HSD17B11 interacts with NAD+ cofactor and is functionally linked to steroidogenic enzymes such as CYP19A1, HSD17B1, AKR1C3, and 5??-reductase (SRD5A2). Disruption of HSD17B11 shifts the balance of estrogens and androgens, altering activation of ESR1 and AR pathways.
In the A-549 lung cancer context, HSD17B11 knockout provides a tool to dissect the contributions of local steroid metabolism to tumor cell behavior. Lung adenocarcinoma cells express steroidogenic enzymes, and intratumoral steroid synthesis may influence proliferation, migration, and drug sensitivity. By eliminating HSD17B11 activity, researchers can investigate how altered E2/E1 ratios and DHT availability impact AR and ER signaling, potentially revealing roles in tumor suppression or oncogenesis. This model supports studies on metabolic reprogramming, hormonal crosstalk in the tumor microenvironment, and identification of vulnerabilities in hormone-dependent signaling axes in non-traditional hormonal cancers.
This polyclonal knockout product is suited for functional assays including LC-MS/MS-based steroid profiling to quantify estrogen and androgen metabolites, western blotting and RT-qPCR for downstream target analysis, and cell proliferation, migration, and invasion assays to assess phenotypic consequences. It also facilitates transcriptomic analyses via RNA-seq to map gene expression changes induced by HSD17B11 loss. For hormone response studies, cells can be challenged with steroid precursors or receptor ligands. For further details or to discuss custom projects, please contact Ascent Research.
