Oncogenic mutations in B-Raf and Kirsten-Ras (K-Ras) are mutually exclusive during human cancer pathogenesis. In an effort to study the biological basis of this epistasis, gene targeting was used to create isogenic sets of human cancer cells differing only in presence or absence of endogenous oncogenic K-Ras or wild-type B-Raf. Whereas cells lacking the K-Ras oncogene were unable to efficiently...

The role of K-ras mutations in the progression of tumors of the ampulla of Vater is not well understood. To study the frequency and timing of K-ras mutations in ampullary tumors, areas of invasive carcinoma and adjacent adenomas were microdissected from paraffin blocks from 96 resected tumors. DNA was extracted, PCR amplification of K-ras exon 1 was performed, and PCR products were sequenced. S...

E-cadherin, as a tumor suppressor, plays an important role for intercellular adhesion involved in metastasis. Although K-Ras is highly expressed in a variety of cancers, the regulation of E-cadherin expression by K-Ras in association with DNA methylation and cell metastasis has not been completely clarified. In this study, E-cadherin expression was repressed in 267B1/K-Ras human epithelial pros...

When overexpressed in primary erythroid progenitors, oncogenic Ras leads to the constitutive activation of its downstream signaling pathways, severe block of terminal erythroid differentiation, and cytokine-independent growth of primary erythroid progenitors. However, whether high-level expression of oncogenic Ras is required for these phenotypes is unknown. To address this issue, we expressed ...

K-Ras proteins transduce signals from membrane-bound receptors via multiple downstream effector pathways and thereby regulate fundamental stem cell processes that affect neoplasia, including proliferation, apoptosis, and differentiation, but their contribution to tumourigenesis is unclear. Because cancers develop from stem cells, we set out to determine the characteristic changes in gene expres...

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Ras(mt) alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part t...

We investigated the presence of K-ras gene mutation in plasma DNA and assessed its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon 12 of the K-ras gene were examined by mutant allele-specific amplification method using DNA extracted from surgical specimens and plasma samples of 21 patients with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21...

Although K-ras is frequently mutated in lung adenocarcinomas, the normal function of K-ras p21 in lung is not known. In two mouse (E10 and C10) and one human (HPL1D) immortalized lung cell lines from peripheral epithelium, we have measured total K-ras p21 and active K-ras p21-GTP during cell proliferation and at growth arrest caused by confluence. In all three cell types, total K-ras p21 increa...

To investigate the role of K-ras mutations in canine non-small cell lung cancer, »etirsi determined the nucleotide sequence of the normal canine K-ras gene and then examined 21 canine lung tumors for acti vating K-ras mutations. Canine K-ras was analyzed by direct sequencing of polymerase chain reaction products generated with oligonucleotide primers derived from the human K-ras sequence. Four...

K-ras is involved in the EGFR pathway that regulates cell survival, motility and proliferation, as well as angiogenesis and metastasis. It is also essential for carcinogenesis. The K-ras mutation status can be used to predict the therapeutic efficacy of targeted drugs such as cetuximab. The aim of this study was to compare K-ras mutation in different types of cancer. Nested and COLD-PCR were us...