Calcyclin gene expression modulation by medroxyprogesterone acetate.
Calcyclin is a cell-cycle-related gene corresponding to a calcium-binding protein whose expression is mainly controlled by platelet-derived growth factor. This paper illustrates medroxyprogesterone acetate (MPA) inhibition of endogenous calcyclin RNA expression of both estrogen-dependent human mammary carcinoma cells and estrogen-independent hamster fibroblasts. Transfection of fragments of the calcyclin promoter driving the chloramphenicol-acetyl-transferase (CAT) gene into hamster fibroblasts was used to evaluate the hormone sensitivity of different promoter regions by considering calcyclin expression at both the RNA and protein level, as evaluated by the CAT assay. A 164 bp promoter fragment showed a good activity that was inhibited by MPA, thereby confirming the results of the observation of endogenous calcyclin gene: smaller fragments, however, required cotransfection of progestin receptor to show full activity, with MPA displaying a stimulatory effect. These findings show that progestin modulation of calcyclin gene expression may be independent of progestin receptors, and that MPA has opposite effects on different promoter regions.
Ghezzo
F
F
Department of Clinical and Biological Sciences, University of Turin, Ospedale San Luigi G., Orbassano(TO), Italy.
Berta
G N
GN
Beccaro
M
M
D'Avolio
A
A
Racca
S
S
Conti
G
G
Di Carlo
F
F
D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D045167:Progesterone Congeners / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000235:genetics; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; D014161:Transduction, Genetic; D014162:Transfection
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human; D012313:RNA; D017258:Medroxyprogesterone Acetate