Progesterone induced expression of alkaline phosphatase is associated with a secretory phenotype in T47D breast cancer cells.
In our previous work we reported on stimulation of a tissue unspecific alkaline phosphatase (liver/bone/kidney, L/B/K) in the human breast cancer cell line T47D by progestins. Here we show that in these cells the synthetic progestin R5020 (Promegestone) induces transcription of a 2.7-kilobase ALP mRNA. In this cel line, maximal induction is reached after 24 hours, decreases to 50% after 72 hours and is sensitive to inhibitors of protein synthesis. The induction of ALP mRNA and enzyme activity is specific for R5020 and dexamethasone and is completely inhibited in the presence of 10(-7) M RU486. When treated with R5020 for 48 hours, T47D cells exhibit a substantially altered phenotype, lipid vacuoles accumulate all over the cytoplasm, conferring to the cells a secretory morphology. This phenotype is associated with increased ALP enzyme activity which is also maximal at 48 hours. This effect is progestin specific since other steroids do not lead to the same macroscopical changes.
Di Lorenzo
D
D
Institute of Chemistry, School of Medicine, University of Brescia, Italy.
Giannì
M
M
Savoldi
G F
GF
Ferrari
F
F
Albertini
A
A
Garattini
E
E
D000469:Alkaline Phosphatase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D001943:Breast Neoplasms; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D011374:Progesterone / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008055:Lipids; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011374:Progesterone; D011397:Promegestone; D000469:Alkaline Phosphatase