The antiproliferative activities of wild-type (wt) p53 are inhibited by mdm2 (murine double minute2) oncogene product. We tested growth suppression activity of p53 14/19, an engineered p53 variant, which does not bind mdm2 and is completely resistant to the inhibition by mdm2. p53 14/19, unlike wt p53, suppressed the growth of cancer cells that contain amplified mdm2 oncogene efficiently by dir...

Previously, it has been demonstrated that thyroid hormone is an important cofactor of the initiation of oncogenesis in viro and in vitro. In order to determine the mechanism of thyroid hormone modulation of the initiation of carcinogenesis we have addressed the hypothesis that thyroid hormone regulates the expression of the critical protooncogene at the time of exposure to the carcinogen, and t...

Oncogene-induced senescence acts as a barrier against tumour formation and has been implicated as the mechanism preventing the transformation of benign melanocytic lesions that frequently harbour oncogenic B-RAF or N-RAS mutations. In the present study we systematically assessed the relative importance of the tumour suppressor proteins p53, p21(Waf1), pRb and p16(INK4a) in mediating oncogene-in...

Cellular and viral oncogenes are usually defined on the basis of their ability to elicit neoplastic transformation. However, oncogene activity has also been implicated in the control of differentiation. We have tested whether transfection of primary cultured granulosa cells with various oncogenes can yield cell lines that maintain their differentiated properties. Primary granulosa cells were pr...

Histone deacetylase inhibitors (HDACIs) cause oncogene‑transformed mammalian cell death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1) and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is involved in HDACI‑mediated oncogene‑transformed mammalian cell death remains unclear. In the present study, H‑ras transformed MCF10A cells were used to in...

The rat leukemia virus (RaLV) is an endogenous retrovirus that is spontaneously released by Sprague-Dawley rat embryo cells. The overall structure of the RaLV genome resembles that of other simple, replication-competent retroviruses, but the sequence of the long terminal repeats (LTR) is unique and unrelated to the known retroviruses. Phylogenetically, the RaLV genome appears to be more closely...

The effects of viral Kirsten ras oncogene expression on the polarized phenotype of MDCK cells were investigated. Stable transformed MDCK cell lines expressing the v-K-ras oncogene were generated via infection with a helper-independent retroviral vector construct. When grown on plastic substrata, transformed cells formed continuous monolayers with epithelial-like morphology. However, on permeabl...

We have investigated the levels of protein encoded by the ras oncogene in normal mouse tissues using an immunoblotting technique. We have found that heart from young or adult NIH or Balb C strains of mice contain high levels of ras protein as compared to lung, liver, spleen, kidney, brain and skeletal muscle tissues from the same animal. Our results indicate that cellular ras expression does no...

Angiogenesis is crucial for embryogenesis, reproduction, and wound healing and is a critical determinant of tumor growth and metastasis. The multifunctional signal transducer Ras is a proto-oncogene and frequently becomes mutated in a variety of human cancers, including angiosarcomas. Regulation of Ras is important for endothelial cell function and angiogenesis. Hyperactivation of Ras is linked...

Pancreatic cancer is genetically complex, and without effective therapy. Mutations in the Kirsten-ras (K-ras) oncogene occur early and frequently (approximately 90%) during pancreatic cancer development and progression. In this context, K-ras represents a potential molecular target for the therapy of this highly aggressive cancer. We now show that a bipartite adenovirus expressing a novel cance...