Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination
Abstract Melanoma is a serious type of skin cancer that originates from melanocytes. Rodent melanoma models have provided valuable insights into melanoma pathology; however, they often lack applicability to humans owing to genetic, anatomical, physiological, and metabolic differences. Herein, we dev...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82554-w |
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| author | Dongjin Oh Nayoung Hong Kiyoung Eun Joohyeong Lee Lian Cai Mirae Kim Hyerin Choi Ali Jawad Jaehyung Ham Min Gi Park Bohye Kim Sang Chul Lee Changjong Moon Hyunggee Kim Sang-Hwan Hyun |
| author_facet | Dongjin Oh Nayoung Hong Kiyoung Eun Joohyeong Lee Lian Cai Mirae Kim Hyerin Choi Ali Jawad Jaehyung Ham Min Gi Park Bohye Kim Sang Chul Lee Changjong Moon Hyunggee Kim Sang-Hwan Hyun |
| author_sort | Dongjin Oh |
| collection | DOAJ |
| description | Abstract Melanoma is a serious type of skin cancer that originates from melanocytes. Rodent melanoma models have provided valuable insights into melanoma pathology; however, they often lack applicability to humans owing to genetic, anatomical, physiological, and metabolic differences. Herein, we developed a transgenic porcine melanoma model that closely resembles humans via somatic cell nuclear transfer (SCNT). Our model features the conditional oncogenes cassettes, TP53R167H and human BRAFV600E, controlled by melanocyte-specific CreER recombinase. After SCNT, transgenic embryos developed normally, with the capacity to develop porcine embryonic stem cells. Seven transgenic piglets with oncogene cassettes were born through embryo transfer. We demonstrated that Cre recombination-mediated oncogene activation remarkably triggered the mitogen-activated protein kinase pathway in vitro. Notably, intradermal injection of 4-hydroxytamoxifen activated oncogene cassettes in vivo, resulting in melanocytic lesions resembling hyperpigmented nevi with increased proliferative properties similar to early human melanomas. This melanoma-inducing system, heritably transmitted to offspring, supports large-scale studies. The novel porcine model provides a valuable tool for elucidating melanoma development and metastasis mechanism, advancing translational medicine, and facilitating preclinical evaluation of new anticancer drugs. |
| format | Article |
| id | doaj-art-bf624f3cb0d34d468b92a6a433795692 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-bf624f3cb0d34d468b92a6a4337956922025-01-12T12:15:27ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-82554-wGeneration of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombinationDongjin Oh0Nayoung Hong1Kiyoung Eun2Joohyeong Lee3Lian Cai4Mirae Kim5Hyerin Choi6Ali Jawad7Jaehyung Ham8Min Gi Park9Bohye Kim10Sang Chul Lee11Changjong Moon12Hyunggee Kim13Sang-Hwan Hyun14Laboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea UniversityDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea UniversityDepartment of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National UniversityCronex Inc.Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National UniversityDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea UniversityLaboratory of Veterinary Embryology and Biotechnology (VETEMBIO), Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National UniversityAbstract Melanoma is a serious type of skin cancer that originates from melanocytes. Rodent melanoma models have provided valuable insights into melanoma pathology; however, they often lack applicability to humans owing to genetic, anatomical, physiological, and metabolic differences. Herein, we developed a transgenic porcine melanoma model that closely resembles humans via somatic cell nuclear transfer (SCNT). Our model features the conditional oncogenes cassettes, TP53R167H and human BRAFV600E, controlled by melanocyte-specific CreER recombinase. After SCNT, transgenic embryos developed normally, with the capacity to develop porcine embryonic stem cells. Seven transgenic piglets with oncogene cassettes were born through embryo transfer. We demonstrated that Cre recombination-mediated oncogene activation remarkably triggered the mitogen-activated protein kinase pathway in vitro. Notably, intradermal injection of 4-hydroxytamoxifen activated oncogene cassettes in vivo, resulting in melanocytic lesions resembling hyperpigmented nevi with increased proliferative properties similar to early human melanomas. This melanoma-inducing system, heritably transmitted to offspring, supports large-scale studies. The novel porcine model provides a valuable tool for elucidating melanoma development and metastasis mechanism, advancing translational medicine, and facilitating preclinical evaluation of new anticancer drugs.https://doi.org/10.1038/s41598-024-82554-wMelanomaTransgenic cancer modelPigTissue-specific activationSomatic cell nuclear transfer |
| spellingShingle | Dongjin Oh Nayoung Hong Kiyoung Eun Joohyeong Lee Lian Cai Mirae Kim Hyerin Choi Ali Jawad Jaehyung Ham Min Gi Park Bohye Kim Sang Chul Lee Changjong Moon Hyunggee Kim Sang-Hwan Hyun Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination Scientific Reports Melanoma Transgenic cancer model Pig Tissue-specific activation Somatic cell nuclear transfer |
| title | Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination |
| title_full | Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination |
| title_fullStr | Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination |
| title_full_unstemmed | Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination |
| title_short | Generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional Cre recombination |
| title_sort | generation of a genetically engineered porcine melanoma model featuring oncogenic control through conditional cre recombination |
| topic | Melanoma Transgenic cancer model Pig Tissue-specific activation Somatic cell nuclear transfer |
| url | https://doi.org/10.1038/s41598-024-82554-w |
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