{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:05:46Z","timestamp":1792044346689,"version":"4.4.0"},"reference-count":30,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82173136"],"award-info":[{"award-number":["82173136"]}]},{"name":"National Natural Science Foundation of China","award":["82203683"],"award-info":[{"award-number":["82203683"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prolactinomas are commonly treated with dopamine receptor agonists (DAs), such as bromocriptine (BRC) and cabergoline (CAB). However, 10\u201330% of patients exhibit resistance to DA therapies. DA resistance is largely associated with reduced dopamine D2 receptor (DRD2) expression, potentially regulated by epigenetic modifications, though the underlying mechanisms are still unclear. Clinical samples were assessed for p300 expression. MMQ and AtT-20 cells were engineered to overexpress either wild-type p300 or a histone acetyltransferase (HAT) domain-mutant form of p300. Mechanistic studies included cell proliferation assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, chromatin immunoprecipitation followed by quantitative PCR, reverse transcription quantitative PCR, and Western blotting. Additionally, an in vivo nude mouse xenograft model was used to confirm the in vitro findings. DAs downregulated p300 through the cAMP-PKA-CREB pathway. Activation of the HAT domain of p300 increased H3K18\/27 acetylation, promoted DRD2 transcription, and worked synergistically with DA to exert anti-tumor effects both in vitro and in vivo. Tanshinone IIA (Tan IIA) upregulated p300 and DRD2, enhancing the therapeutic efficacy of BRC. These findings highlight the role of p300 in regulating DRD2 transcription in DA-resistant prolactinomas. Combining Tan IIA with BRC may offer a promising strategy to overcome DA resistance.<\/jats:p>","DOI":"10.3390\/ijms252312483","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:46:11Z","timestamp":1732164371000},"page":"12483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Activation of p300 Enhances the Sensitivity of Pituitary Adenomas to Dopamine Agonist Treatment by Regulating the Transcription of DRD2"],"prefix":"10.3390","volume":"25","author":[{"given":"Sihan","family":"Li","sequence":"first","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingbo","family":"Li","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanji","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-3634","authenticated-orcid":false,"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linpeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Huang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional 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