title: Regulation of protein kinase C delta by estrogen in the MCF-7 human breast cancer cell line.
abstract: We have previously shown that estrogen up-regulates expression of protein kinase C (PKC) delta in the rat and rabbit corpus luteum as well as in luteinized rat granulosa primary cell cultures. To determine whether a similar regulation of the PKC delta isoform by estrogen occurred in another estrogen responsive system, we investigated the estrogen receptor positive MCF-7 human breast cancer cells. In a characterization of PKC isoforms in MCF-7 cells we determined that PKC delta was the predominant PKC isoform. However in contrast to the effect of estrogen on PKC delta expression in ovarian cells, estrogen treatment of MCF-7 cells resulted in a significant decrease in PKC delta protein and mRNA expression in a time and dose dependent manner. Treatment of MCF-7 cells with 10(-10)-10(-8) M estrogen for 7 days down-regulated specifically PKC delta mRNA and protein while expression of other PKC isoforms was unchanged. The opposite regulation of PKC delta expression in ovarian and breast cancer cells prompted us to evaluate the type of estrogen receptor present in both cell types. Results showed that luteinized rat granulosa cells expressed predominantly estrogen receptor beta while the MCF-7 cells expressed predominantly estrogen receptor alpha and barely detectable levels of estrogen receptor beta. These results suggest that the differential ability of estrogen to regulate PKC beta expression could potentially be a result of differential signaling through the two estrogen receptor subtypes.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shanmugam
authors.forename: N L
authors.initials: NL
authors.lastname: Krett
authors.forename: E T
authors.initials: ET
authors.lastname: Maizels
authors.forename: R E
authors.initials: RE
authors.lastname: Cutler
authors.forename: C A
authors.initials: CA
authors.lastname: Peters
authors.forename: L M
authors.initials: LM
authors.lastname: Smith
authors.forename: M L
authors.initials: ML
authors.lastname: O'Brien
authors.forename: O K
authors.initials: OK
authors.lastname: Park-Sarge
authors.forename: S T
authors.initials: ST
authors.lastname: Rosen
authors.forename: M
authors.initials: M
authors.lastname: Hunzicker-Dunn
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D003338:Corpus Luteum / Q000201:enzymology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006107:Granulosa Cells / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D006656:Protamine Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D051745:Protein Kinase C-delta; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D007527:Isoenzymes; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol; C051781:ICI 164384; C497260:Prkcd protein, rat; D006656:Protamine Kinase; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta