Analysis of endogenous and exogenous tumor upregulated promoter expression in canine tumors
| Autor: | Payal Agarwal, Bradley Schuler, Bruce F. Smith, Abdul Mohin Sajib, Maninder Sandey, Samantha Morici |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Skin Neoplasms Lymphoma Genetic enhancement Gene Expression Endogeny Lung and Intrathoracic Tumors Madin Darby Canine Kidney Cells Hematologic Cancers and Related Disorders 0302 clinical medicine Neoplasms Breast Tumors Medicine and Health Sciences Gene Regulatory Networks Dog Diseases Promoter Regions Genetic Skin Tumors Regulation of gene expression Multidisciplinary Prostate Cancer Prostate Diseases Hematology Up-Regulation Gene Expression Regulation Neoplastic Oncology Nephrology Renal Cancer 030220 oncology & carcinogenesis Medicine Research Article Cell type Science Urology Dermatology Biology Transfection Research and Analysis Methods 03 medical and health sciences Dogs Cell Line Tumor Breast Cancer Genetics Animals Telomerase reverse transcriptase Molecular Biology Techniques E2F Molecular Biology Cancers and Neoplasms Biology and Life Sciences Promoter Genitourinary Tract Tumors 030104 developmental biology Cell culture Cancer research |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 11, p e0240807 (2020) |
| ISSN: | 1932-6203 |
| Popis: | Gene therapy is a promising treatment option for cancer. However, its utility may be limited due to expression in off-target cells. Cancer-specific promoters such as telomerase reverse transcriptase (TERT), survivin, and chemokine receptor 4 (CXCR4) have enhanced activity in a variety of human and murine cancers, however, little has been published regarding these promoters in dogs. Given the utility of canine cancer models, the activity of these promoters along with adenoviral E2F enhanced E1a promoter (EEE) was evaluated in a variety of canine tumors, both from the endogenous gene and from exogenously administered constructs. Endogenous expression levels were measured for cTERT, cSurvivin, and cCXCR4 and were low for all three, with some non-malignant and some tumor cell lines and tissues expressing the gene. Expression levels from exogenously supplied promoters were measured by both the number of cells expressing the construct and the intensity of expression in individual cells. Exogenously supplied promoters were active in more cells in all tumor lines than in normal cells, with the EEE promoter being most active, followed by cTERT. The intensity of expression varied more with cell type than with specific promoters. Ultimately, no single promoter was identified that would result in reliable expression, regardless of the tumor type. Thus, these findings imply that identification of a pan-cancer promoter may be difficult. In addition, this data raises the concern that endogenous expression analysis may not accurately predict exogenous promoter activity. |
| Databáze: | OpenAIRE |
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