Regulation of estrogen receptor-alpha expression in MCF-7 cells by taxol.
Results presented in this study demonstrate that treatment of MCF-7 cells with taxol resulted in induction of estrogen receptor-alpha (ER alpha) gene transcription with a subsequent increase in ER alpha mRNA; this effect was promoter specific since taxol did not affect total transcription in MCF-7 cells and lacked an effect on transcription of the human acidic ribosomal phosphoprotein protein PO, progesterone receptor, and pS2 genes. In contrast to the increase in transcription of the ER alpha gene, taxol inhibited translation of the ER alpha mRNA. This effect is also transcript specific since taxol did not alter total protein synthesis and did not affect the concentration of progesterone receptor protein in the cell. The overall result of taxol treatment was to decrease the concentration of ER alpha protein in the MCF-7 cells. Evidence is presented that the effects of taxol on ER alpha gene transcription may be mediated through the induction of p53.
Martin
M B
MB
Department of Oncology, Vincent T Lombardi Cancer Center, Georgetown University, Washington DC 20057, USA.
Angeloni
S V
SV
Garcia-Morales
P
P
Sholler
P F
PF
Castro-Galache
M D
MD
Ferragut
J A
JA
Saceda
M
M
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D017239:Paclitaxel / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D013268:Stimulation, Chemical; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D017239:Paclitaxel