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• W2022043561 abstract "Objectives: Our aim was to examine how certain signal transduction pathways influence the regulation of hormone-dependent kallikrein (KLK) gene expression in androgen-sensitive breast cancer cell lines. Methods: We used the breast cancer cell lines T47D and BT474, treated with steroid hormones or various pathway inhibitors. KLKs were quantified by ELISA. RT-PCR, Western blots and immunoprecipitations were used to assess transcript and protein levels. Results:PSA, KLK10, KLK11, KLK13 and KLK14 are upregulated upon androgen stimulation in the T47D cell line. The expression of PSA, KLK10 and KLK11 was repressed by the MEK1/2 inhibitor U0126 and the PI3K inhibitor Wortmannin in the presence of the hormone, thus implicating the RAS/MEK/ERK and PI3K/AKT signaling pathways in regulating hormone-dependent KLK gene activation. Analysis of inhibitor-treated cells revealed changes in c-MYC expression with a pattern parallel to KLK gene expression. Chromatin immunoprecipitations identified androgen-dependent recruitment of specific transcription factors to the KLK proximal promoters, including c-MYC binding to PSA and KLK11. Conclusion: The hormone-specific upregulation of PSA, KLK10 and KLK11 in the breast cancer cell line T47D is dependent on major intracellular signaling pathways. This work provides a new dimension to the regulation of these cancer-related genes and the potential for new therapeutic targeting strategies." @default.
• W2022043561 created "2016-06-24" @default.
• W2022043561 creator A5013465456 @default.
• W2022043561 creator A5084226800 @default.
• W2022043561 date "2008-01-01" @default.
• W2022043561 modified "2023-10-17" @default.
• W2022043561 title "Intracellular Signaling Pathways Regulate Hormone-Dependent Kallikrein Gene Expression" @default.
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• W2022043561 doi "https://doi.org/10.1159/000135686" @default.
• W2022043561 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18515984" @default.
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