Progesterone and estradiol effects on SRC-1 and SRC-3 expression in human astrocytoma cell lines

Progesterone (P₄) and estradiol (E₂) regulate many cell functions through their interaction with specific intracellular receptors, which require the participation of coactivators such as SRC-1 and SRC-3 for enhancing their transcriptional activity. Coactivator expression is altered in many cancers and in some of them their expression is regulated by P₄ and E₂. In this study, we determined progesterone and estrogen receptor isoform expression in two human astrocytoma cell lines with different evolution grade (U373, grade III; and D54, grade IV) by Western Blot. We studied the role of P₄ and E₂ on SRC-1 and SRC-3 expression in U373 and D54 cell lines by RT–PCR and Western blot. In U373 cells, P₄ did not modify SRC-1 expression, but in D54 cells it increased SRC-1 mRNA expression after 12 h of treatment without significant changes after 24 h. P₄ also increased SRC-1 protein content after 24 h, but reduced it after 48 h. E₂ did not change SRC-1 expression in any cell line. SRC-3 expression was not regulated by either E₂ or P₄. Our data suggest that SRC-1 and SRC-3 expression is differentially regulated by sex steroid hormones in astrocytomas and that P₄ regulates SRC-1 expression depending on the evolution grade of human astrocytoma cells.