NIH3T3 cells overexpressing CD98 heavy chain resist early G1 arrest and apoptosis induced by serum starvation

Abstract

CD98 is a heterodimeric glycoprotein of 125‐kDa, which consists of a 90‐kDa heavy chain (hc) subunit and 35‐kDa to 55‐kDa light chain (lc) subunits. It is strongly expressed on the surface of proliferating normal cells and almost all tumor cells. To investigate the participation of CD98 in cellular proliferation and malignant transformation, we analyzed cell‐cycle progression of NIH3T3 clones transfected with cDNA of human CD98hc. Although NIH3T3 and control transfectant cells grown to the subconfluent state were arrested in the G0/G1 phase by serum starvation, considerable portions of CD98hc‐transfected cells resided at S and G2/M phases. Under serum‐starved and confluent conditions, significant fractions (20–25%) of NIH3T3 and control transfectant cells contained less than 2n content DNA, indicating occurrence of apoptosis, whereas no apoptotic cells were detected in CD98hc‐transfectant cells. Under serum‐starved conditions, a marked increase in the levels of cyclin D1 and cyclin E and a decrease in p16 were observed in CD98hc‐transfectant cells. The reverse was true for NIH3T3 and control transfectant cells. Our results suggest that resistance to G1 arrest and apoptosis by CD98 overexpression are associated with high G1‐cyclins and low p16 levels. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02304.x, 2012)

CD98hc as a marker of radiotherapy-resistant cancer stem cells in head and neck squamous cell carcinoma

“…CD98 is a heterodimer comprising heavy and light chains. The heavy chain binds to β-integrin and plays an important role in integrin signal amplification, cell proliferation, survival, migration, and adhesion [20][21][22], and the light chain is an amino acid transporter LAT1 that maintains rapid cell proliferation and enhanced intracellular metabolism in cancer cells. In this context, CD98hc functions as a co-factor stabilizing LAT1 and xCT [23].…”

Integrative discovery of CD98 as a melanoma biomarker

“…(Cantor and Ginsberg, 2012). Originally described by Haynes et al in 1981 as an antigen on proliferating lymphocytes (Haynes et al, 1981), CD98 has since been shown to be overexpressed in human embryonic stem cells and various carcinoma cell lines (Hara et al, 2012). Additional work using monoclonal antibodies against CD98 revealed a role in proliferation of cancer cell lines that is propagated via the activity of the PI3K/AKT/mTOR pathway (Feral et al, 2005;Masuko et al, 2011).…”

MicroRNA-223 promotes mast cell apoptosis by targeting the insulin-like growth factor 1 receptor

“…2A . Previous studies have shown that serum starvation can effectively induce cell apoptosis ( 32 , 33 ). In the current study, serum starvation conditions were induced on cultured mast cells for 24 h in order to initiate cell apoptosis.…”