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This study aims to integrate immunotherapy and suicide gene therapy for breast cancer treatment. The cytokines\n                    <jats:italic>IL\u20102<\/jats:italic>\n                    and\n                    <jats:italic>GM\u2010CSF<\/jats:italic>\n                    , which are crucial in orchestrating immune responses against cancer, are the focal points of investigation. This study focused on the co\u2010expression of these cytokines alongside apoptin, a promising protein derived from chicken anemia virus, via the bidirectional survivin promoter (pAIG).\n                  <\/jats:p>\n                  <jats:p>\n                    The constructed vectors were transfected into MCF\u20107 cells, which resulted in a significant increase in gene expression. Compared with individual cytokine and apoptin vectors (pIG and pA), the pAIG vector exhibited superior efficacy, reducing cell viability and inducing apoptosis (31.7%) at 72 h post\u2010transfection. Exploration of the interaction of apoptin revealed its association with the human PIK3R1 protein, which interacts with both cytokines, contributing to the inhibition of cell viability. Leveraging the survivin promoter for co\u2010expression presents a promising avenue for targeted breast cancer gene therapy, potentially disrupting intricate signaling networks involved in cancer progression. This study provides valuable insights into the synergistic effects of\n                    <jats:italic>IL\u20102<\/jats:italic>\n                    ,\n                    <jats:italic>GM\u2010CSF<\/jats:italic>\n                    , and apoptin co\u2010expression, offering a compelling approach to advancing breast cancer treatment. These findings contribute to the broader landscape of cancer gene therapy, emphasizing the potential of combining immunomodulatory agents and gene\u2010directed approaches to improve therapeutic outcomes.\n                  <\/jats:p>","DOI":"10.1111\/aji.70226","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T15:21:13Z","timestamp":1778512873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Bidirectional Survivin Promoter Enhances IL\u20102, GM\u2010CSF, and Apoptin Co\u2010expression for Breast Cancer Gene Therapy"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5705-7107","authenticated-orcid":false,"given":"Omid","family":"Barzegari","sequence":"first","affiliation":[{"name":"Department of Human Genetics Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Medical Cellular &amp; Molecular Research Center Golestan University of Medical Sciences  Gorgan Iran"},{"name":"AryaTinaGene (ATG) Biopharmaceutical Company  Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ghadimi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Golestan University of Medical Sciences  Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-4368","authenticated-orcid":false,"given":"Fatemeh T.","family":"Shamsabadi","sequence":"additional","affiliation":[{"name":"Medical Cellular &amp; Molecular Research Center Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Department of Biotechnology Golestan University of Medical Sciences  Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Golalipour","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Medical Cellular &amp; Molecular Research Center Golestan University of Medical Sciences  Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-8282","authenticated-orcid":false,"given":"Majid","family":"Shahbazi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Medical Cellular &amp; Molecular Research Center Golestan University of Medical Sciences  Gorgan Iran"},{"name":"Department of Biotechnology Golestan University of Medical Sciences  Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00437-9"},{"issue":"21","key":"e_1_2_12_3_1","first-page":"1330","article-title":"Gene Therapy as an Emerging Therapeutic Approach to Breast Cancer: New Developments and Challenges","volume":"32","author":"Sheikh\u2010Hosseini M.","year":"2021","journal-title":"Human Gene Therapy"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1527600"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2018.0019"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0328-y"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10020141"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101921-044122"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02905"},{"key":"e_1_2_12_10_1","first-page":"3259","article-title":"Anti\u2010Colorectal Cancer Effect of Interleukin\u20102 and Interferon\u2010\u03b2 Fusion Gene Driven by Carcinoembryonic Antigen Promoter","volume":"9","author":"Wang Y.","year":"2016","journal-title":"OncoTargets and Therapy"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2020.1814620"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179376"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02249-2"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02909"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14122606"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1558678"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01638-1"},{"key":"e_1_2_12_18_1","volume-title":"Combination of Chemotherapy and Cytokine Therapy in Treatment of Cancers","author":"Malvicini M."},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01164-5"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00524"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-015-1567-5"},{"issue":"5","key":"e_1_2_12_22_1","first-page":"2818","article-title":"Recombinant Adenoviruses Expressing Apoptin Suppress the Growth of MCF\u20117 Breast Cancer Cells and Affect Cell Autophagy","volume":"41","author":"Chen S.","year":"2019","journal-title":"Oncology Reports"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00940-1"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2022.914311"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009734.2019.1623351"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34075"},{"key":"e_1_2_12_27_1","first-page":"123","volume-title":"PANTHER Pathway: An Ontology\u2010Based Pathway Database Coupled With Data Analysis Tools. 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