Retroviral-mediated transduction of p53 gene increases TGF-beta expression in a human glioblastoma cell line.
Transforming growth factor-beta (TGF-beta) has been implicated as a potent growth regulator; the degree of responses to it, whether positive or negative, generally correlates with the stage of cell differentiation in various cell types. We examined the effect of the p53 gene, which participates in the control of cell-cycle progression, on the expression of human TGF-beta. The human glioblastoma cell line SNB-19, which expresses the latent form of TGF-beta, was transfected with a retroviral vector containing wild-type p53 (wt-p53) or p53 with a mutation (mut-p53) at codon 273. Stable G418-resistant SNB-19 clones were isolated. The growth kinetics of wt-p53 transfectants were suppressed compared with those of parental cells, vector transfectants, or mut-p53 transfectants, as assayed by growth-curve measurements and 3H-thymidine incorporation; however, RNA dot blot and Western blot analyses demonstrated that wt-p53 and mut-p53 transfectants expressed higher amounts of TGF-beta 1 and TGF-beta 2 mRNA and intracellular TGF-beta isoform proteins, respectively, than parental cells. By means of the biological assay for active TGF-beta (Mv1Lu cell-growth-inhibition assay), we observed that both transfectants produced active TGF-beta, whereas the parental cells produced only the latent form. These results suggest that, while only the wt-p53 gene inhibits tumor-cell progression, both wt-p53 and codon 273-mutated p53 can cause increased TGF-beta expression.
Fujiwara
T
T
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Mukhopadhyay
T
T
Cai
D W
DW
Morris
D K
DK
Roth
J A
JA
Grimm
E A
EA
D001483:Base Sequence; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta