title: 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.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Hara
authors.forename: Shiho
authors.initials: S
authors.lastname: Ueda
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ohno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Yagi
authors.forename: Shogo
authors.initials: S
authors.lastname: Okazaki
authors.forename: Rieko
authors.initials: R
authors.lastname: Kawahara
authors.forename: Takechi
authors.initials: T
authors.lastname: Masayuki
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Kazue
authors.initials: K
authors.lastname: Masuko
authors.forename: Takashi
authors.initials: T
authors.lastname: Masuko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007158:Immunologic Techniques; D051379:Mice; D041681:NIH 3T3 Cells / Q000378:metabolism*; D044967:Serum
chemical_list: D018797:Cell Cycle Proteins; D027282:Fusion Regulatory Protein 1, Heavy Chain