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Imatinib, a tyrosine kinase inhibitor, can slow tumor formation by targeting c\u2010KIT, an oncogenic receptor tyrosine kinase protein over\u2010expressed in PCa cases. However, Imatinib has no effect on tr\u2010KIT, a truncated form of c\u2010KIT, which is over\u2010expressed in PCa and is associated with neoplastic transformation. In this study, it is aimed to answer whether the anti\u2010proliferative efficacy of Imatinib on PCa cells could be enhanced by inhibition of tr\u2010KIT specific transcription factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>For this purpose, gene expression analysis and cell viability assays were performed in LNCaP prostate cancer cells to investigate the effects of inhibition of transcription factors controlling tr\u2010KIT expression (YY1 and NFYA) in combination with Imatinib administration. As a result, YY1 and NFYA were identified as tr\u2010KIT\u2010specific transcription factors and found that their knockdown increased the effectiveness of Imatinib mesylate treatment on LNCaP cells. The study also analyzed the gene expression changes of c\u2010KIT, FYN, PLC\u03b31, and SAM68 genes and found that SAM68 expression decreased with NFYA and YY1 knockdown, suggesting the existence of other unknown mediators in the tr\u2010KIT pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>All in all, this study demonstrates that tr\u2010KIT may be a potential pharmacological target for prostate cancer treatment and that inhibition of the transcription factors YY1 and NFYA may enhance the efficacy of Imatinib. SAM68 was found to be the most affected protein by the treatments, guiding future research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gcc.70063","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T09:53:36Z","timestamp":1753523616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tr\u2010<scp>KIT<\/scp> Downstream Regulation by <scp>YY1<\/scp> and <scp>NFYA<\/scp> Transcription Factors Knockdown in Prostate Cancer Cells"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6733-9848","authenticated-orcid":false,"given":"Sercan","family":"Ergun","sequence":"first","affiliation":[{"name":"Department of Medical Biology Faculty of Medicine, Ondokuz Mayis University  Samsun 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