Isolation and characterization of genes associated with the anti-tumor activity of glucocorticoids.
Treatment of ST1 rat glioma cells with glucocorticoid hormones leads to complete reversion of their transformed phenotype and loss of their tumorigenic potential. In order to study the molecular basis of the anti-tumor activity of these hormones, we isolated glucocorticoid-regulated cDNA sequences associated with ST1 cells' phenotypic reversion, using suppression subtractive hybridization (SSH). DNA sequencing of the subtracted cDNA pool, cloned into the pBluescript vector, revealed three widely expressed, well known negative growth regulators, namely, thrombospondin 1, cyclin G and tyrosine phosphatase CL100, as primary targets of glucocorticoid hormones. Additionally, a gene recently described in human brain, NRP/B (nuclear restricted protein in brain) that associates with p110Rb in induction of neuronal differentiation and a new truncated transcript of the tenascin-X gene family, are also shown to be up-regulated by glucocorticoids. The products of these genes are strong candidates to be important players in glucocorticoids anti-tumor activity.
Vedoy
Cleber Giovane
CG
Instituto de Qui;mica, Universidade de São Paulo, C.P. 26.077, 05513-970 SP, São Paulo, Brazil.
Sogayar
Mari Cleide
MC
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006824:Hybridization, Genetic; D006854:Hydrocortisone / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010641:Phenotype; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D005938:Glucocorticoids; D006854:Hydrocortisone