The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma.

FBXW7 is reported to be a tumor suppressor gene, and the functional inactivation of FBXW7 has been reported in various human tumors. In this study, we investigated the FBXW7 gene in human thymoma; although no mutations were evident, a significantly high frequency of methylation in the FBXW7 beta-form promoter was observed in types B1 or higher (P=0.014).

Promoter hypermethylation is not the major mechanism for inactivation of the FBXW7 beta-form in human gliomas.

FBXW7 has been reported to be a candidate tumor suppressor gene on 4q31. Three isoforms (alpha-form, beta-form, and gamma-form) of FBXW7 are produced from mRNAs with distinct 5' exons. Our previous study identified the specific suppression of the mRNA expression of the FBXW7 beta-form in human gliomas.

siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma.

Objective: To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of EGFR on lung cancer.

Methods: We analyzed mutations in EGFR, KRAS, TP53, and ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines.

The FBXW7 beta-form is suppressed in human glioma cells.

FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins.