Transcriptional control of thymidine kinase gene expression by estrogen and antiestrogens in MCF-7 human breast cancer cells.
The mechanism by which estrogen and antiestrogens modulate cytoplasmic thymidine kinase (TK) activity has been studied in MCF-7 cells. Using a cloned cDNA probe for human TK, we have identified a single 1500-nucleotide transcript as the cytoplasmic TK-mRNA in MCF-7 cells. In normally cycling or synchronously growing cells, the level of this mRNA maximally increased 2-3-fold after 24 h of estradiol-17 beta (E2) stimulation and decreased below control level in the presence of antiestrogens. Neither E2 nor antiestrogens altered the size of TK-mRNA. Hormonal regulation of TK-mRNA paralleled changes in TK enzyme activity and [3H]thymidine incorporation. Using endogenous nuclear run-off transcription to investigate the expression of the human TK gene, we demonstrate that TK-mRNA levels were regulated by transcriptional control. Modulation of TK gene activity during the process of estrogen stimulation or antiestrogen inhibition was not accompanied by changes in the methylation pattern at internal sites of the TK gene. These results suggest a transcriptional control of human TK gene by E2 and antiestrogens in MCF-7 cells.
A
A
Kasid
N E
NE
Davidson
E P
EP
Gelmann
M E
ME
Lippman
D000546:Amanitins / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology*; D002453:Cell Cycle; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008745:Methylation; D011759:Pyrrolidines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics*; D013997:Time Factors
D000546:Amanitins; D004965:Estrogen Antagonists; D004967:Estrogens; D011759:Pyrrolidines; D012333:RNA, Messenger; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; D012313:RNA; C025430:LY 117018; D004247:DNA; D013937:Thymidine Kinase; D013936:Thymidine