KRAS NF-kappa B is involved in the development of zinc
resistance and reduced curability in prostate cancer

J 2014

KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer

HOLUBOVÁ, Monika; Martina AXMANOVÁ; Jaromír GUMULEC; Martina RAUDENSKÁ; Markéta SZTALMACHOVÁ et al.

Základní údaje

Originální název

KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer

Autoři

HOLUBOVÁ, Monika ; Martina AXMANOVÁ; Jaromír GUMULEC; Martina RAUDENSKÁ ; Markéta SZTALMACHOVÁ; Petr BABULA; Vojtěch ADAM; René KIZEK a Michal MASAŘÍK

Vydání

Metallomics, Cambridge, Royal Society of Chemistry, 2014, 1756-5901

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.585

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/14:00076568

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

CITRATE METABOLISM; EPITHELIAL-CELLS; CARCINOMA-CELLS; DNA-DAMAGE; T-ANTIGEN; EXPRESSION; METALLOTHIONEIN; TRANSPORTER; APOPTOSIS; GENES

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 11. 2014 14:24, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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.

Návaznosti

MUNI/A/1003/2013, interní kód MU

Název: Molekulární patofyziologie vybraných komplexních nemocí

Investor: Masarykova univerzita, Molekulární patofyziologie vybraných komplexních nemocí, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

HOLUBOVÁ, Monika; Martina AXMANOVÁ; Jaromír GUMULEC; Martina RAUDENSKÁ; Markéta SZTALMACHOVÁ; Petr BABULA; Vojtěch ADAM; René KIZEK a 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, roč. 6, č. 7, s. 1240-1253. ISSN 1756-5901. Dostupné z: https://doi.org/10.1039/c4mt00065j.

@article{1199029,
   author = {Holubová, Monika and Axmanová, Martina and Gumulec, Jaromír and Raudenská, Martina and Sztalmachová, Markéta and Babula, Petr and Adam, Vojtěch and Kizek, René and Masařík, Michal},
   article_location = {Cambridge},
   article_number = {7},
   doi = {https://doi.org/10.1039/c4mt00065j},
   keywords = {CITRATE METABOLISM; EPITHELIAL-CELLS; CARCINOMA-CELLS; DNA-DAMAGE; T-ANTIGEN; EXPRESSION; METALLOTHIONEIN; TRANSPORTER; APOPTOSIS; GENES},
   language = {eng},
   issn = {1756-5901},
   journal = {Metallomics},
   title = {KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer},
   volume = {6},
   year = {2014}
}

TY  - JOUR
ID  - 1199029
AU  - Holubová, Monika - Axmanová, Martina - Gumulec, Jaromír - Raudenská, Martina - Sztalmachová, Markéta - Babula, Petr - Adam, Vojtěch - Kizek, René - Masařík, Michal
PY  - 2014
TI  - KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer
JF  - Metallomics
VL  - 6
IS  - 7
SP  - 1240-1253
EP  - 1240-1253
PB  - Royal Society of Chemistry
SN  - 17565901
KW  - CITRATE METABOLISM
KW  - EPITHELIAL-CELLS
KW  - CARCINOMA-CELLS
KW  - DNA-DAMAGE
KW  - T-ANTIGEN
KW  - EXPRESSION
KW  - METALLOTHIONEIN
KW  - TRANSPORTER
KW  - APOPTOSIS
KW  - GENES
N2  - 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.
ER  -

HOLUBOVÁ, Monika; Martina AXMANOVÁ; Jaromír GUMULEC; Martina RAUDENSKÁ; Markéta SZTALMACHOVÁ; Petr BABULA; Vojtěch ADAM; René KIZEK a Michal MASAŘÍK. KRAS NF-kappa B is involved in the development of zinc resistance and reduced curability in prostate cancer. \textit{Metallomics}. Cambridge: Royal Society of Chemistry, 2014, roč.~6, č.~7, s.~1240-1253. ISSN~1756-5901. Dostupné z: https://doi.org/10.1039/c4mt00065j.

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