Author:
Lønne Gry Kalstad,Cornmark Louise,Zahirovic Iris Omanovic,Landberg Göran,Jirström Karin,Larsson Christer
Abstract
Abstract
Background
Protein kinase C (PKC) isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes.
Results
In two cohorts of primary breast cancers, PKCα levels correlated to estrogen and progesterone receptor negativity, tumor grade, and proliferative activity, whereas PKCδ and PKCε did not correlate to clinicopathological parameters. Patients with PKCα-positive tumors showed poorer survival than patients with PKCα-negative tumors independently of other factors. Cell line studies demonstrated that PKCα levels are high in MDA-MB-231 and absent in T47D cells which proliferated slower than other cell lines. Furthermore, PKCα silencing reduced proliferation of MDA-MB-231 cells. PKCα inhibition or downregulation also reduced cell migration in vitro.
Conclusions
PKCα is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Reference42 articles.
1. Vargo-Gogola T, Rosen JM: Modelling breast cancer: one size does not fit all. Nat Rev Cancer. 2007, 7: 659-672. 10.1038/nrc2193
2. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn van de M, Jeffrey SS: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098
3. Newton AC: Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev. 2001, 101: 2353-2364. 10.1021/cr0002801
4. Ways DK, Kukoly CA, deVente J, Hooker JL, Bryant WO, Posekany KJ, Fletcher DJ, Cook PP, Parker PJ: MCF-7 breast cancer cells transfected with protein kinase C- α exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype. J Clin Invest. 1995, 95: 1906-1915. 10.1172/JCI117872
5. Chisamore MJ, Ahmed Y, Bentrem DJ, Jordan VC, Tonetti DA: Novel antitumor effect of estradiol in athymic mice injected with a T47D breast cancer cell line overexpressing protein kinase Cα. Clin Cancer Res. 2001, 7: 3156-3165.
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