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Protein kinase C and mammary cell differentiation: involvement of protein kinase C alpha in the induction of beta-casein expression.
- Source :
-
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research [Cell Growth Differ] 1994 Mar; Vol. 5 (3), pp. 239-47. - Publication Year :
- 1994
-
Abstract
- Treatment of HC11 mouse mammary epithelial cells with the lactogenic hormones dexamethasone, insulin, and prolactin (DIP) leads to cellular differentiation and production of the milk protein beta-casein. The following experimental evidence suggests the involvement of protein kinase C (PKC) in DIP induced signal transduction. Down-regulation of PKC by 12-O-tetradecanoylphorbol-13-acetate or addition of CGP 41251, a selective inhibitor of PKC, inhibited beta-casein protein expression induced by DIP in HC11 cells. This inhibition occurs at the level of transcription, since the DIP mediated activation of a beta-casein promoter-luciferase reporter construct or of mammary gland specific factor (MGF), an essential transcription factor for beta-casein promoter activity, was also inhibited by CGP 41251. Inhibition or down-regulation of PKC reduced the activation of MGF by prolactin as well. PKC-alpha, the only conventional PKC isoform expressed in HC11 cells, is most likely involved in the DIP induced beta-casein expression. (a) Only PKC-alpha and PKC-epsilon are down-regulated by 12-O-tetradecanoylphorbol-13-acetate whereas PKC-delta and PKC-zeta are not. (b) Of the PKC isoforms expressed in HC11 cells, CGP 41251 inhibits PKC-alpha more potently than PKC-delta, PKC-epsilon, and PKC-zeta. The IC50 for the inhibition of beta-casein synthesis, MGF activation, and beta-casein promoter activity by CGP 41251 correlated well with the IC50 of PKC-alpha inhibition. (c) Finally, only PKC-alpha translocated to membrane fractions after DIP or prolactin treatment. Taken together, these data indicate that PKC-alpha plays an important role in the signaling pathway activated by prolactin during beta-casein induction.
- Subjects :
- Alkaloids pharmacology
Amino Acid Sequence
Animals
Base Sequence
Cell Differentiation drug effects
Cell Line
Dexamethasone pharmacology
Epithelial Cells
Epithelium metabolism
Female
Gene Expression Regulation physiology
Insulin pharmacology
Isoenzymes antagonists & inhibitors
Mammary Glands, Animal drug effects
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Pregnancy
Prolactin pharmacology
Protein Kinase C antagonists & inhibitors
Protein Kinase C-alpha
Tetradecanoylphorbol Acetate pharmacology
Caseins biosynthesis
Isoenzymes physiology
Mammary Glands, Animal cytology
Mammary Glands, Animal metabolism
Protein Kinase C physiology
Staurosporine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1044-9523
- Volume :
- 5
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 8018556