Methylation-mediated silencing of G0S2 has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 opposes oncogene-induced transformation using G0S2-null immortalized mouse embryonic fibroblasts (MEFs). G0S2-null MEFs were readily transformed with HRAS or EGFR treatment compared to wildtype MEFs. Importantly, restoration of G0S2 reversed HRAS-driven transformation. G0S2 is known to regulate fat metabolism by attenuating adipose triglyceride lipase (ATGL), but repression of oncogene-induced transformation by G0S2 was independent of ATGL inhibition. Gene expression analysis revealed that an upregulation of gene signatures associated with transformation, proliferation, and MYC targets in G0S2-null MEFs. RNAi-mediated ablation and pharmacologic inhibition of MYC abrogated oncogene-induced transformation of G0S2-null MEFs. Furthermore, we found that G0S2 was highly expressed in normal breast tissues compared to malignant tissue. Intriguingly, high levels of G0S2 were also associated with a decrease in breast cancer recurrence rates, especially in estrogen receptor-positive subtypes, and overexpression of G0S2 repressed the proliferation of breast cancer cells in vitro. Taken together, these findings indicate that G0S2 functions as a tumor suppressor in part by opposing MYC activity, prompting further investigation of the mechanisms by which G0S2 silencing mediates MYC-induced oncogenesis in other malignancies.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfqZ7L
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Abstract Epilepsy is a serious neurological disorder which disturbs the common activities of a human brain. It is detected with the help o...
-
The main idea behind this work was demonstrated in a form of a new thermoelectrochromic sensor on a flexible substrate using graphene as an ...
-
Tetracycline Repressors (TetRs) modulate multi-drug efflux pathways in several pathogenic bacteria. In Streptomyces, they additionally regul...
-
Abstract There are many unanswered questions about giant cell tumor (GCT) treatment and not enough attention is paid to the biomechanics o...
-
Bearing faults are the biggest single source of motor failures. Artificial Neural Networks (ANNs) and other decision support systems are wid...
-
Nowadays, sound classification applications are becoming more common in the Wireless Acoustic Sensor Networks (WASN) scope. However, these a...
-
The paper proposes a multicriteria decision analysis (MCDA) framework for a comparative evaluation of nuclear waste management strategies ta...
-
Tuberculosis (TB) is one of the leading causes of death worldwide, especially in developing countries. Neonatal BCG vaccination occurs in va...
-
Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopat...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου