The mutated K-ras gene is involved in approximately 30% of human cancers. In order to search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we performed microarray and proteomics (LC/ESI-MS/MS) analysis. Genes (RAB27b RAS family, IL-1RA, IL-33, chemokine ligand 6, epiregulin, EGF-like domain and cathepsin) related to cancer development (Wnt signaling pathway) an...

During the course of in vitro screening of agents which are preferentially active against ras oncogene-expressed cells, a new anthracycline (identified as 2-demethylsteffimycin D) and a heptaene (possibly a new member of partricins) were isolated from microbial fermentation broths. Among known compounds tested, 5-fluorouracil, 5-fluorodeoxyuridine and oxanosine showed high selectivity towards r...

We have previously described the inhibition of glucocorticoid-dependent transcription from the mouse mammary tumor virus long terminal repeat promoter by products of the H-ras and v-mos oncogenes. We have studied the effects of conditional oncogenes on expression of glucocorticoid-dependent indicator genes. Expression of the glucocorticoid-dependent transcription of the tyrosine aminotransferas...

It is now widely accepted that human neoplasms arise as a result of a sequence of mutations affecting the structure of genes involved in growth control. Identifying the nature of such genetic mutations in thyroid neoplasms and their prevalence in the various tumor phenotypes is critical to the understanding of their pathogenesis. Mutational activation of ras oncogenes has been associated with h...

Increasing evidence has pointed to activated type I interferon signaling in tumors. However, the molecular basis for such activation and its role in tumorigenesis remain unclear. In the current studies, we report that activation of type I interferon (IFN) signaling in tumor cells is primarily due to elevated secretion of the type I interferon, IFN-β. Studies in oncogene-transformed cells sugges...

Oncogene inactivation in both clinical targeted therapies and conditional transgenic mouse cancer models can induce significant tumor regression associated with the robust induction of apoptosis. Here we report that in MYC-, RAS-, and BCR-ABL-induced acute lymphoblastic leukemia (ALL), apoptosis upon oncogene inactivation is mediated by the same pro-apoptotic protein, BIM. The induction of BIMi...

An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5′-CGCCCGTGCCCTGCGCCCGCAACCCGA-3′ (herein referred as iHRAS), forms an vitro but its exact was unknown. member RAS proto-oncogene family. About 19 % US cancer patients carry mutations genes. We solved iHRAS at 1.77 Å resolution. reveals that folds into double ...

Resistance of tumors to irradiation or chemotherapeutic agents is thought to be one of the reasons why patients who present with early malignancies may not be cured. Much is now known about the molecular mechanisms that underlie drug resistance, but until recently little was known about genetic contributions to radiation resistance. Some evidence now links oncogenes, particularly the ras family...

The activated Ras oncogene can transform various mammalian cells and has been implicated in development of a high population of malignant human tumors. Recent studies suggest that generation of reactive oxygen species such as superoxide and H(2)O(2) is involved in cell transformation by the activated Ras. However, the nature of an oxidase participating in Ras-transformation is presently unknown...

Antipain (AP; 50 Mg/ml) inhibits transformation of NIH3T3 cells after transfection with an activated H-ras oncogene. To determine whether AP effects on transformation are associated with alterations in oncogene expression, NIH3T3 cells were cotransfected with an activated H-ras oncogene and the selectable marker gene uph. and gene expression was quantified. Fifty percent of geneticin-resistant ...