The AKR1C2 Knockout SiHa Cell Line is a CRISPR/Cas9-edited knockout cell line featuring targeted disruption of the AKR1C2 gene in the human cervical squamous cell carcinoma SiHa cell line. This stable loss-of-function model is provided as a characterized knockout pool, ready for downstream functional studies.
The SiHa cell line is a well-characterized model of HPV16-positive cervical cancer, derived from a squamous cell carcinoma. SiHa cells express the viral oncoproteins E6 and E7, which functionally inactivate the tumor suppressors p53 and pRb, respectively. This genetic background recapitulates key features of cervical carcinogenesis, including deregulated cell cycle control and enhanced invasive potential, providing a relevant context for studying hormone-responsive pathways.
AKR1C2 encodes an aldo-keto reductase that catalyzes the NADPH-dependent reduction of ketosteroids, converting progesterone to the less active 20??-hydroxyprogesterone and generating 5??-androstane-3??,17??-diol (3??-diol) from androgens. The enzyme??s activity is regulated by upstream factors including the androgen receptor, progesterone receptor, IL-6, TNF-??, and Nrf2, and it functions within a network encompassing AKR1C1, AKR1C3, HSD17B2, SRD5A1, PTGS2, and HPGD. Through interaction with NADPH and steroid hormones, AKR1C2 also reduces prostaglandin D2, thereby influencing prostaglandin F2?? levels and linking steroidogenic and prostanoid pathways. Disruption of AKR1C2 thus perturbs local hormone metabolism, potentially impacting diverse signaling cascades.
In the HPV16-positive, p53-deficient, and pRb-inactivated SiHa cervical cancer model, AKR1C2 knockout provides a unique tool to investigate how altered androgen and progesterone metabolism influences tumor cell behavior. Given the reliance of cervical cancer cells on steroid hormones for proliferation and survival, loss of AKR1C2 may unmask dependencies on specific hormone pathways and reveal therapeutic vulnerabilities. This model facilitates the study of AKR1C2??s role in modulating cell growth, invasion, and response to hormonal stimuli within a relevant oncogenic background.
The AKR1C2 Knockout SiHa Cell Line is ideal for a wide range of functional studies, including quantitative hormone metabolism analysis by LC-MS, assessment of cell viability via MTT or BrdU assays, Transwell migration and invasion experiments, and drug sensitivity profiling. It enables mechanistic dissection of AKR1C2 in cervical cancer progression, evaluation of prostaglandin signaling in tumorigenesis, and exploration of AKR1C2 as a target for hormone-related cancers. For more information, please contact Ascent Research.
