Previous reports have indicated that mutations of the RAS oncogenes are not associated with the chronic phase of Philadelphia chromosome-positive chronic myelogenous leukemia (Ph1+ CML). However, further studies were needed to determine their association with Ph1- CML and chronic myelomonocytic leukemia (CMML). Therefore, 6 patients with Ph1- CML who were also negative for BCR rearrangements (P...

The thyroid hormone triiodothyronine (T3) has a profound effect on growth, differentiation, and metabolism in higher organisms. Here we demonstrate that T3 inhibits ras-induced proliferation in neuroblastoma cells and blocks induction of cyclin D1 expression by the oncogene. The hormone, at physiological concentrations, strongly antagonizes the transcriptional response mediated by the Ras/mitog...

Persistent revertants have been generated from NIH 3T3 cells transformed by an activated human Ha-ras gene after short-term gamma interferon treatment in the presence of the cardiac aminoglycoside ouabain. Normal fibroblastlike morphology and anchorage dependence are restored in revertants. Tumorigenicity in nude mice is abolished. The revertants continue to express high steady-state levels of ...

Transformation of fibroblast cells by v-abl oncogene involved overexpression of the c-myc (5) or of the cellular protein p53 (6). Two proto-oncogenes, cmyc and c-K-ras, have been shown to cooperate in the transformation of secondary rat embryo fibroblasts (7). Oncogenic activation of c-myc occurs mainly through constituve and elevated expression of its gene product and generally requires cooper...

STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only virus-encoded protein found to associate with cellular ras and activate ras signal transduction pathways. To investigate an important role for ras signal transduction in STP-dependent growth transformation, we constructed recombinant strains of HVS C488 in which the STP-C488 oncogene was replaced with cellular nor...

An activated K-ras oncogene was detected by transfection in NIH 3T3 cells and by Southern blot analysis in 6 of 12 rat skin tumors induced by ionizing radiation. The DNA from 10 of the 12 tumors also showed c-myc gene amplification and restriction polymorphisms. Evidence for tissue specificity was observed in patterns of oncogene activation, with each of three clear cell carcinomas exhibiting a...

Activation of ras proto-oncogenes occurs frequently in vivo in chemically induced rodent tumours, including rat hepatomas induced by aflatoxin B1. This study examines the in vitro activation of a human ras gene by this mycotoxin. A plasmid containing the human Ha-ras proto-oncogene, together with a neomycin resistance gene (pECneo), was incubated in vitro with a microsomal system generating afl...

To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting approximately 4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significan...

Ras activating mutations result in constitutive activation of Ras signalling pathways and occur in 30% of human malignancies. K-ras encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in lung, pancreatic and colorectal cancers. Using RT-PCR we examined their expression in normal adult human tissues and addressed whether K...