MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype.
Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha, and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.
Ways
D K
DK
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
Kukoly
C A
CA
deVente
J
J
Hooker
J L
JL
Bryant
W O
WO
Posekany
K J
KJ
Fletcher
D J
DJ
Cook
P P
PP
Parker
P J
PJ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology / Q000648:ultrastructure; D002448:Cell Adhesion; D002453:Cell Cycle; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics*; D051571:Protein Kinase C-alpha; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
D007527:Isoenzymes; D011994:Recombinant Proteins; C496628:PRKCA protein, human; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha