TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Brandenstein, Melanie von
A1  - Straube, Julia
A1  - Loeser, Heike
A1  - Ozretic, Luca
A1  - Fries, Jochen W. U.
T1  - Endothelin-1 induced Mxi-2/Ago2 complex formation resulting in 5P536 downregulation promoting breast cancer development
JF  - Life Sciences
N2  - Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors.
Y1  - 2013
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-10754
SN  - 0024-3205
SS  - 0024-3205
U6  - https://doi.org/10.1016/j.lfs.2013.12.041
DO  - https://doi.org/10.1016/j.lfs.2013.12.041
N1  - Abstracts from the Thirteenth International Conference on Endothelin (ET-13), Tokyo, September 8-11, 2013
VL  - 93
IS  - 25–26
SP  - e3
PB  - Elsevier
ER  -