PKCα expression is a marker for breast cancer aggressiveness

Abstract

BackgroundProtein 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.ResultsIn 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.ConclusionsPKCα is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression.

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC subversion induces up-regulation of PKC II expression in B lymphocytes

“…PKCa is up-regulated in breast, gastric, prostate and brain cancers, suggesting that it contributes to tumorigenesis, 24,25 and higher expression levels have been linked with the aggressiveness and invasive capacity of breast cancer cells. 26,27 However, PKCa expression is down-regulated in epidermal, pancreatic, and colon cancers [28][29][30][31][32] and CLL 21 suggesting that PKCa can also function as a tumor suppressor. This was demonstrated in mouse models for colon cancer, in which a reduction in PKCa expression was observed in carcinogen-induced colon cancer, 32 and APC min/+ mice.…”

Protein Kinase C (PKC) Isozymes and Cancer

“…For example, PKC has been used as a biomarker for GIST, especially GIST that is immunohistochemically negative for KIT and/or DOG1 [176][177][178]. Furthermore, PKC has been used as a diagnostic biomarker for ovarian [500] and NSCLC [306], while PKC and PKC II have been used for breast cancer [49,60] and diffuse large B-cell lymphoma (DLBCL; also known as nonHodgkin's lymphoma) [354][355][356], respectively. However, in spite of usefulness of immunohistochemical biomarkers, cancer biomarkers in blood, urine, feces, or saliva have received much greater interest recently as they are easier to sample and handle; the amount of pain is reduced in patients during sampling, and the detection techniques are, overall, much less invasive compared to the analysis of tissue samples.…”

“…Overexpression of PKC in MCF-7 cells alters 5-and 3-integrin expression by translational and posttranslational mechanisms, respectively, leading to the increased metastatic capacity of cancer cells [59]. Thus, PKC expression in breast cancer cells may be closely associated with poor prognosis and survival [49,60].…”

Transient PKCα shuttling to the immunological synapse is governed by (DGK)ζ and regulates L-selectin shedding

“…siRNA oligonucleotides used to silence PKCa have been described (Lønne et al, 2010) and siRNA to silence DGKf corresponds to the same region as the shRNA to DGKf. Jurkat T cells in logarithmic growth were transfected with 25 mg plasmid DNA or with siRNA oligonucleotides by electroporation as above.…”