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 inhibited human breast cancer xenograft, T61; one showing 100% homology to the human BAC clone RP11-112E16, the other 100% homology to the human CPR3/DNJ3 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. Treatment of T61 tumors with tamoxifen, leading to static tumor growth, also increased 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 mRNA expression, indicating that regulation of the gene products is mediated through the ER. The association between growth inhibition and BAC clone RP11-112E16 or CPR3/DNJ3 mRNA expression was supported by high expression of both gene products in brain tissue. Further investigations are ongoing to clarify the biological function of these two gene products.
Ohlsson
H
H
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.
Brünner
N
N
Engelholm
L H
LH
Lundholt
B K
BK
Weidle
U
U
Briand
P
P
Lykkesfeldt
A E
AE
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009857:Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C494645:DNAJA2 protein, human; D004967:Estrogens; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D013629:Tamoxifen