CRISPR/Cas9-mediated gene knockout of ARID1A promotes primary progesterone resistance by downregulating progesterone receptor B in endometrial cancer cells.

CRISPR/Cas9-mediated gene knockout of ARID1A promotes primary progesterone resistance by downregulating progesterone receptor B in endometrial cancer cells. Oncol Res. 2019 May 09;: Authors: Wang H, Tang Z, Li T, Liu M, Li Y, Xing B Abstract Medroxyprogesterone (MPA) is used for the conservative treatment of endometrial cancer. Unfortunately, progesterone resistance seriously affects its therapeutic effect. The purpose of the current study was to investigate the influence of deletion of AT-Rich Interactive Domain 1A (ARID1A) in progesterone resistance in Ishikawa cells. Ablation of ARID1A was conducted through the CRISPR/Cas9 technology. Acquired progesterone-resistant Ishikawa (Ishikawa-PR) cells were generated by chronic exposure of Ishikawa cells to MPA. The sensitivity of the parental Ishikawa, Ishikawa-PR and ARID1A-deficient cells to MPA and/or LY294002 was determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. In addition, Western blot analysis and reversetranscription-polymerase chain reaction was performed to evaluate the mRNA and protein expression levels of ARID1A, progesterone receptor B (PRB) and P-AKT. Both Ishikawa-PR and ARID1A knockout cells showed insensitivity to MPA, downregulation of PRB and hyperphosphorylation of AKT compared to the parental Ishikawa cells. Pretreatment with LY294002 significantly enhanced the ability of MPA to suppress proliferation and to induce apoptosis in the p...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research