Cell lines modified with these genetic lesions recapitulated tipifarnib resistance <i>in vivo</i> This study demonstrates the feasibility of targeting Ras membrane association in cancers <i>in vivo</i> and predicts combination therapies that confer additional benefit.<b>Significance:</b> Tipifarnib effectively inhibits oncogenic HRAS-driven tumorigenesis and abrogating adaptive signaling improves responses.
Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS.
These results demonstrate that PPARβ/δ promotes senescence to inhibit tumorigenesis and provide new mechanistic insights into HRAS-induced cellular senescence.
The data strongly support the role of selection in determining HRAS mutation levels in sperm, and hence the occurrence of CS, but we also found differences from the mutation pattern in tumorigenesis.
Abnormal methylation of the HRAS gene may be an early event during urocystic tumorigenesis and may be further used as a cancer biomarker in bladder tissue for early diagnosis and a potential therapeutic target.
In a mouse model of HRAS Q61L-mediated skin carcinogenesis, the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations, and this growth was blocked by concomitant treatment with a MEK inhibitor.
Our results indicate that both EGFR and HRAS mutations are rare events in the carcinogenesis of cutaneous SCC, and therefore, only a small subgroup of patients will benefit from the screening for EGFR mutations in the run-up to targeted therapies with EGFR inhibitors.
We found that TRAIL expression is consistently downregulated in HRAS(G12V)-transformed cells in stepwise tumorigenesis models derived from four different tissues due to DNA hypermethylation of CpG clusters within the TRAIL promoter.
High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis.
We conclude that the non-B DNA structural polymorphism detected in human tumors near the c-Ha-ras VNTR is a self-perpetuating epigenetic mark that manifests itself spontaneously during breast carcinogenesis in a methylation hot spot.
In this review, the focus is on current knowledge regarding the relationship between Kras2 and experimental mouse lung carcinogenesis, especially from the aspect of disease predisposition.
The present study was conducted to examine the effects of DAG oil on carcinogenesis in c-Ha-ras proto-oncogene transgenic (Tg) rats administered 4-nitroquinoline 1-oxide (4NQO, 10 ppm) in their drinking water for 10 weeks for initiation of mainly upper digestive organs.
Our recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-kappaB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis.
This evidence suggests that constitutive activation of MAPK1 synergistically induced by frequent mutation of KRAS2 and the loss of function of DUSP6 plays key roles in pancreatic carcinogenesis and progression.
All together, co-existence of Aurora-A overexpression and Ha-ras mutation suggests a possible additively effect on the tumorigenesis of bladder cancer.
An activating point mutation in codon 12 of the HRAS gene was the first somatic point mutation identified in a human cancer and established the role of somatic mutations as the common driver of oncogenesis.
To this end, we tried to establish an animal model using the human c-Ha-ras proto-oncogene-carrying transgenic (Tg) rats and the carcinogen 4-nitroquinoline 1-oxide (4-NQO).4-NQO (20 p.p.m.) was administered to Tg and non-Tg rats for 8 weeks in their drinking water, and then the occurrence of tongue carcinogenesis was compared during the experimental period of 22 weeks.