Wild-type p53 tumor suppressor gene restores differentiation of human squamous carcinoma cells but not the response to transforming growth factor beta.
In order to clarify the role of the p53 tumor suppressor gene in controlling growth and differentiation of human epithelial cells, we transfected a wild-type p53 complementary DNA, driven by a dexamethasone-inducible mouse mammary tumor virus promoter, into SqCC/Y1 human head-and-neck squamous carcinoma cells. When treated with dexamethasone, 2 of 8 independent clones that contained integrated vector sequences expressed wild-type p53-specific mRNA as well as nuclear p53 protein. The highest p53 expressor (SqCC/Y1.53.5) was as resistant to inhibition of cell growth by transforming growth factor beta as control transfectants. Furthermore, these cells continued to proliferate in medium containing the combination of 2 mM Ca2+ and 10% (v/v) fetal bovine serum, which normally induces terminal differentiation in primary keratinocytes. However, under these same conditions, two of the essential proteins required for the formation of the cornified cell envelope were induced. First, in SqCC/Y1.53.1 and -.5 cells, the activity of membrane-associated keratinocyte-specific transglutaminase I increased to 3- to 5-fold higher levels than in control transfectants. Second, in SqCC/Y1.53.1 and -.5 cells, the envelope precursor, involucrin, increased to 5 to 8 times the levels attained in control transfectants. Thus, reexpression of wild-type p53 does not restore responsiveness of SqCC/Y1 carcinoma cells to growth inhibition but allows cells to reexpress the proteins required for the assembly of the cornified cell envelope.
Brenner
L
L
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Muñoz-Antonia
T
T
Vellucci
V F
VF
Zhou
Z L
ZL
Reiss
M
M
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D016158:Genes, p53; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta