Academic Journal
The role of chromodomain helicase DNA binding protein 1 (CHD1) in promoting an invasive prostate cancer phenotype
| العنوان: | The role of chromodomain helicase DNA binding protein 1 (CHD1) in promoting an invasive prostate cancer phenotype |
|---|---|
| المؤلفون: | Kareddula, Aparna, Medina, Daniel J., Petrosky, Whitney, Dolfi, Sonia, Tereshchenko, Irina, Walton, Kelly, Aviv, Hana, Sadimin, Evita, Tabakin, Alexandra L., Singer, Eric A., Hirshfield, Kim M. |
| المساهمون: | C. R. Bard Foundation, National Institutes of Health, Walter and Louise Sutcliffe Foundation |
| المصدر: | Therapeutic Advances in Urology ; volume 13 ; ISSN 1756-2872 1756-2880 |
| بيانات النشر: | SAGE Publications |
| سنة النشر: | 2021 |
| الوصف: | Background: Prostate cancer (PCa) phenotypes vary from indolent to aggressive. Molecular subtyping may be useful in predicting aggressive cancers and directing therapy. One such subtype involving deletions of chromodomain helicase DNA binding protein 1 ( CHD1), a tumor suppressor gene, are found in 10–26% of PCa tumors. In this study, we evaluate the functional cellular effects that follow CHD1 deletion. Methods: CHD1 was knocked out (KO) in the non-tumorigenic, human papillomavirus 16 (HPV16)-immortalized prostate epithelial cell line, RWPE-1, using CRISPR/Cas9. In vitro assays such as T7 endonuclease assay, western blot, and sequencing were undertaken to characterize the CHD1 KO clones. Morphologic and functional assays for cell adhesion and viability were performed. To study expression of extracellular matrix (ECM) and adhesion molecules, a real-time (RT) profiler assay was performed using RWPE-1 parental, non-target cells (NT2) and CHD1 KO cells. Result: Compared to parental RWPE-1 and non-target cells (NT2), the CHD1 KO cells had a smaller, rounder morphology and were less adherent under routine culture conditions. Compared to parental cells, CHD1 KO cells showed a reduction in ECM and adhesion molecules as well as a greater proportion of viable suspension cells when cultured on standard tissue culture plates and on plates coated with laminin, fibronectin or collagen I. CHD1 KO cells showed a decrease in the expression of secreted protein acidic and rich in cysteine (SPARC), matrix metalloproteinase 2 (MMP2), integrin subunit alpha 2 (ITGA2), integrin subunit alpha 5 (ITGA5), integrin subunit alpha 6 (ITGA6), fibronectin (FN1), laminin subunit beta-3 precursor (LAMB3), collagen, tenascin and vitronectin as compared to parental and NT2 cells. Conclusion: These data suggest that in erythroblast transformation specific (ETS) fusion-negative, phosphatase and tensin homolog ( PTEN) wildtype PCa, deletion of CHD1 alters cell-cell and cell-matrix adhesion dynamics, suggesting an important role for CHD1 in the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/17562872211022462 |
| الاتاحة: | https://doi.org/10.1177/17562872211022462 https://journals.sagepub.com/doi/pdf/10.1177/17562872211022462 https://journals.sagepub.com/doi/full-xml/10.1177/17562872211022462 |
| Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.A0496948 |
| قاعدة البيانات: | BASE |
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