Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors
Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subje...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-08-01
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| Series: | Breast Cancer: Basic and Clinical Research |
| Online Access: | https://doi.org/10.1177/11782234221111374 |
| _version_ | 1811339409137598464 |
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| author | Bryan McClellan Tommy Pham Brittany Harlow Gabby Lee Duan Quach Christopher Jolly Andrew Brenner Linda deGraffenried |
| author_facet | Bryan McClellan Tommy Pham Brittany Harlow Gabby Lee Duan Quach Christopher Jolly Andrew Brenner Linda deGraffenried |
| author_sort | Bryan McClellan |
| collection | DOAJ |
| description | Purpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element–binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody. Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter. Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer. |
| first_indexed | 2024-04-13T18:26:13Z |
| format | Article |
| id | doaj.art-fc05823491154e1a92ec210b700f6884 |
| institution | Directory Open Access Journal |
| issn | 1178-2234 |
| language | English |
| last_indexed | 2024-04-13T18:26:13Z |
| publishDate | 2022-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Breast Cancer: Basic and Clinical Research |
| spelling | doaj.art-fc05823491154e1a92ec210b700f68842022-12-22T02:35:14ZengSAGE PublishingBreast Cancer: Basic and Clinical Research1178-22342022-08-011610.1177/11782234221111374Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic FactorsBryan McClellanTommy PhamBrittany HarlowGabby LeeDuan QuachChristopher JollyAndrew BrennerLinda deGraffenriedPurpose: The objective of this study is to determine the impact of exposure to obesity-related systemic factors on fatty acid synthase enzyme (FASN) expression in breast cancer cells. Methods: MCF-7 breast cancer cells were exposed to sera from patients having obesity or not having obesity and subjected to quantitative reverse transcription polymerase chain reaction (RT-qPCR). Subsequent MTT and colony-forming assays using both MCF-7 and T-47D cells exposed to sera and treated with or without FASN inhibitor, TVB-3166, were used. MCF-7 cells were then treated with insulin and the sterol regulatory element–binding protein (SREBP) processing inhibitor, betulin, prior to analysis of FASN expression by quantitative RT-qPCR and western blot. Insulin-induced SREBP-FASN promoter binding was analyzed by chromatin immunoprecipitation with an anti-SREBP antibody. Results: In response to sera exposure (body mass index [BMI] >30) there was an increase in FASN expression in breast cancer cells. Furthermore, treatment with the FASN inhibitor, TVB-3166, resulted in a decreased breast cancer cell survival and proliferation while increasing apoptosis upon sera exposure (BMI >30). Insulin-exposed MCF-7 cells exhibited an increased FASN messenger RNA and protein expression, which is abrogated upon SREBP inhibition. In addition, insulin exposure induced enhanced SREBP binding to the FASN promoter. Conclusions: Our results implicate FASN as a potential mediator of obesity-induced breast cancer aggression and a therapeutic target of patients with obesity-induced breast cancer.https://doi.org/10.1177/11782234221111374 |
| spellingShingle | Bryan McClellan Tommy Pham Brittany Harlow Gabby Lee Duan Quach Christopher Jolly Andrew Brenner Linda deGraffenried Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors Breast Cancer: Basic and Clinical Research |
| title | Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors |
| title_full | Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors |
| title_fullStr | Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors |
| title_full_unstemmed | Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors |
| title_short | Modulation of Breast Cancer Cell FASN Expression by Obesity-Related Systemic Factors |
| title_sort | modulation of breast cancer cell fasn expression by obesity related systemic factors |
| url | https://doi.org/10.1177/11782234221111374 |
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