Unknown

Dataset Information

0

Increased susceptibility of breast cancer cells to stress mediated inhibition of protein synthesis.


ABSTRACT: Protein synthesis is a tightly controlled process, and its deregulation plays an important role in tumorigenesis. Protein synthesis remains poorly understood with very few well-identified validated targets for therapeutic purposes. In this study, we use nitric oxide (NO), which suppresses protein synthesis by inactivating eukaryotic initiation factor 2-alpha (eIF2-alpha), to examine the mechanism by which low and high oxidative stress inhibits protein synthesis. In breast cancer cells, low NO stress induced heme-regulated inhibitor (HRI) activation, which facilitated gradual decline in short half-life proteins. High NO stress induced HRI and protein kinase R (PKR) activation, leading to a sharp decline in protein synthesis as accessed by a decline in short and long half-life proteins and dramatic morphologic changes. In contrast, human mammary epithelial (HME) and Ras transfected untransformed HME (MCF-10A1 neo N) cells were less susceptible to NO-induced inhibition of protein synthesis and cytostasis. Our results suggest that NO-induced cytostasis in breast cancer cells was due to PKR activation and increased phosphorylation of eIF2-alpha, whereas the reduced susceptibility of normal mammary epithelial cells to NO could be due to the inaccessibility of PKR, which is bound to inhibitor p58.

SUBMITTER: Pervin S 

PROVIDER: S-EPMC4416651 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Increased susceptibility of breast cancer cells to stress mediated inhibition of protein synthesis.

Pervin Shehla S   Tran An H AH   Zekavati Shaghayegh S   Fukuto Jon M JM   Singh Rajan R   Chaudhuri Gautam G  

Cancer research 20080601 12


Protein synthesis is a tightly controlled process, and its deregulation plays an important role in tumorigenesis. Protein synthesis remains poorly understood with very few well-identified validated targets for therapeutic purposes. In this study, we use nitric oxide (NO), which suppresses protein synthesis by inactivating eukaryotic initiation factor 2-alpha (eIF2-alpha), to examine the mechanism by which low and high oxidative stress inhibits protein synthesis. In breast cancer cells, low NO st  ...[more]

Similar Datasets

2023-06-14 | GSE234460 | GEO
| S-ECPF-GEOD-37210 | biostudies-other
| S-EPMC3409022 | biostudies-literature
| S-EPMC4631207 | biostudies-literature
2012-04-11 | E-GEOD-37210 | biostudies-arrayexpress
| PRJNA981480 | ENA
| S-EPMC3633900 | biostudies-literature
| S-EPMC5239519 | biostudies-literature
| S-EPMC6544980 | biostudies-literature
| S-EPMC10849468 | biostudies-literature