Non-small cell lung cancer (NSCLC) is a heterogeneous disease, caused by the presence of different clinically relevant molecular subtypes. Genetic mutations are emerging as potential biomarkers of response and treatment selection in patients with NSCLC. Over the past few years, activating mutations of epidermal growth factor receptor (EGFR) have been recognized as the most important predictor o...

Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomark...

Background—Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/ INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies. Aims—To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver. Methods—The status of p16 was evaluated in 41 cholangiocarcinomas by methyla...

BACKGROUND The genes RAS and BRAF have been shown to be frequently mutated in human thyroid carcinomas. The aim of this study was to genotype a cohort of 55 sporadic papillary thyroid carcinomas (PTC) and 44 sporadic medullary thyroid carcinomas (MTC) for the K-RAS codon 12 and BRAF codon 600 mutations. MATERIALS AND METHODS K-RAS and BRAF mutations were characterized by an enhanced polymeras...

OBJECTIVE Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathway...

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...

The proto-oncogenic Ras isoforms (H, N, and K) have a C-terminal CAAX motif and undergo the same post-translational processing steps, although they traffic to the plasma membrane through different routes. Previously, we have shown that overexpression of the deubiquitinating enzyme USP17 inhibits H-Ras localization to the plasma membrane. Now we report that whereas H-Ras and N-Ras were unable to...

The Ras-ERK pathway is frequently up-regulated in colorectal cancer. We analyzed the clinical-pathological correlation of K-Ras mutation and phospho-ERK expression in colorectal cancer. K-Ras mutations were detected in only 32.5% (41/126) of the colorectal cancer cases, while all cancers were positive for phospho-ERK staining. Colorectal cancer with wild-typeK-Ras and low phospho-ERK expression...

In the majority of breast cancers, overexpression and hyperactivation of Ras in the tumor microenvironment play significant role in promoting cancer cell growth, angiogenesis, and metastasis. We have previously shown that vascular endothelial growth factor (VEGF) expression in triple negative breast cancer cells is regulated, at least in part, by SAF-1 (serum amyloid A activating factor 1) tran...

Estrogens are considered as a major risk factor of endometrial cancer. In this study, we identified a mechanism of tumorigenesis in which K-Ras protein is stabilized via estrogen signaling through the ER-α36 receptor. PKCδ was shown to stabilize K-Ras specifically via estrogen signaling. Estrogens stabilize K-Ras via inhibition of polyubiquitylation-dependent proteasomal degradation. Estrogen-i...