HOLUBOVÁ, Monika, Martina AXMANOVÁ, Jaromír GUMULEC, Martina RAUDENSKÁ, Markéta SZTALMACHOVÁ, Petr BABULA, Vojtěch ADAM, René KIZEK and Michal MASAŘÍK. KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer. Metallomics. Cambridge: Royal Society of Chemistry, 2014, vol. 6, No 7, p. 1240-1253. ISSN 1756-5901. Available from: https://dx.doi.org/10.1039/c4mt00065j.
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Basic information
Original name KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer
Authors HOLUBOVÁ, Monika (203 Czech Republic, belonging to the institution), Martina AXMANOVÁ (203 Czech Republic, belonging to the institution), Jaromír GUMULEC (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Markéta SZTALMACHOVÁ (203 Czech Republic, belonging to the institution), Petr BABULA (203 Czech Republic), Vojtěch ADAM (203 Czech Republic), René KIZEK (203 Czech Republic) and Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution).
Edition Metallomics, Cambridge, Royal Society of Chemistry, 2014, 1756-5901.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10600 1.6 Biological sciences
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 3.585
RIV identification code RIV/00216224:14110/14:00076568
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1039/c4mt00065j
UT WoS 000338638000009
Keywords in English CITRATE METABOLISM; EPITHELIAL-CELLS; CARCINOMA-CELLS; DNA-DAMAGE; T-ANTIGEN; EXPRESSION; METALLOTHIONEIN; TRANSPORTER; APOPTOSIS; GENES
Tags EL OK
Tags International impact, Reviewed
Changed by Changed by: Ing. Mgr. Věra Pospíšilíková, učo 9005. Changed: 25/11/2014 14:24.
Abstract
Zinc(II) ions are important components of many proteins and are involved in numerous cellular processes such as apoptosis or drug resistance. Prostate cancer has a unique relationship with zinc(II) ions. However, the relationship was examined only in short-term zinc(II) treatments. Therefore, the aim of this study was to create zinc-resistant prostatic cell lines at various stages of the disease (22Rv1 and PC-3) and a normal prostate epithelium (PNT1A) using a long-term zinc exposure. Consequently, the expression profile of the following genes was analyzed: BAX, Bcl-2, Beclin-1, CFLAR, HIF1 alpha, KRAS, mTOR, MT1A, MT2A, NF-kappa B1, p53, survivin, ZIP1, ZnT-1. The resistance was verified using the MTT test; on average a 1.35-fold lower zinc(II) toxicity (higher IC50) was determined in zinc(II)-resistant cells. The associated resistance to cisplatin was also determined; IC50 for cisplatin was 1.52-fold higher. With regard to the gene expression profiles, our results indicate that differential mechanisms participate in the short-term zinc toxicity regulation and long-term resistance; the short-term treatment was associated with MT2A (p < 0.001), ZnT-1 (p < 0.001), and MT1A (p < 0.03) and the long-term resistance was associated particularly with NF-kappa B1 (p < 0.001), CFLAR (p < 0.001), KRAS (p < 0.001), p53 (p < 0.002), survivin (p = 0.02), ZIP1 (p = 0.002), BAX (p = 0.005), and HIF1 alpha (p = 0.05). Therefore, the KRAS-PI3K-NF-kappa B pathway is expected to play a crucial role in the regulation of zinc resistance. In summary, compared to previous studies, identical mechanisms of resistance were demonstrated on multiple cell lines, both non-tumor and tumorous, derived both from primary and advanced secondary sites.
Links
MUNI/A/1003/2013, interní kód MUName: Molekulární patofyziologie vybraných komplexních nemocí
Investor: Masaryk University, Category A
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