Identification of two estrogen regulated genes associated with growth regulation of human breast cancer

We have identified two estrogen regulated gene products in the E-2 growth i nhibited human breast cancer xenograft, T61, one showing 100% homology to t he human BAC clone RP11-112E16, the other 100% homology to the human CPR3/D NJ3 gene, Verification by Northern blot analyses showed an up-regulation of the BAC clone RP11-112E16 and the CPR3/DNJ3 mRNAs upon E-2 treatment, Trea tment of T61 tumors with tamoxifen. leading to static tumor growth, also in creased the expression of the BAC clone RP11-112E16 and the CPR3/DNJ3 mRNAs . A similar association between growth inhibition and BAC clone RP11-112E16 and CPR3/DNJ3 mRNA induction was observed in MCF-7 cells treated with ICI 182.780. In MCF-7 cells, treatment with E-2 resulted in growth stimulation concomitant with a decrease in the BAC clone RP11-112E16 and CPR3/DNJ3 mRNA expression. Treatment with a combination of E-2 and ICI 182.780 abolished the anti-estrogen induced increase in BAC clone RP11-112E16 and CPR3/DNJ3 m RNA expression, indicating that regulation of the gene products is mediated through the ER. The association between growth inhibition and BAC clone RP 11-112E16 or CPR3/DNJ3 mRNA expression was Supported by high expression of both gene products in brain tissue, Further investigations are ongoing to c larify the biological function of these two gene products. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.