Protein kinase Cε as a cancer marker and target for anticancer therapy

Totoń, Ewa; Ignatowicz, Ewa; Skrzeczkowska, Karolina; Rybczyńska, Maria

doi:10.1016/s1734-1140(11)70395-4

Cited by 47 publications

(43 citation statements)

References 89 publications

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“…Overexpression of PKCε has been detected in numerous cancer types, including colon, breast, stomach, prostate, thyroid and lung and it is considered to be an important marker of negative disease outcome. Suppression of the gene encoding PKCε using antisense cDNA, inhibition of PKCε using RNAi or inhibition of PKCε using translocation-inhibitory peptides may be further developed into novel cancer treatment strategies (Toton et al, 2011).…”

Section: Breast Cancermentioning

confidence: 99%

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

França-Botelho¹,

Ferreira²,

França³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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In this review, we describe the patterns of known immunological components in breast milk and examine the relationship between breastfeeding and reduced risk of breast cancer. The top risk factors for breast cancer are a woman's age and family history, specifically having a first-degree relative with breast cancer. Women that have a history of breastfeeding have been shown to have reduced rates of breast cancer. Although the specific cause has not been elucidated, previous studies have suggested that breastfeeding reduces the risk of breast cancer primarily through two mechanisms: the differentiation of breast tissue and reduction in the lifetime number of ovulatory cycles. In this context, one of the primary components of human milk that is postulated to affect cancer risk is alpha-lactalbumin. Tumour cell death can be induced by HAMLET (a human milk complex of alpha-lactalbumin and oleic acid). HAMLET induces apoptosis only in tumour cells, while normal differentiated cells are resistant to its effects. Therefore, HAMLET may provide safe and effective protection against the development of breast cancer. Mothers should be encouraged to breastfeed their babies because the complex components of human milk secretion make it an ideal food source for babies and clinical evidence has shown that there is a lower risk of breast cancer in women who breastfed their babies.

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Section: Breast Cancermentioning

confidence: 99%

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

França-Botelho¹,

Ferreira²,

França³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…PKC isoenzymes can be categorized into three groups by their structural and biochemical properties: the conventional or classical ones (α, βI, βII, and γ) require Ca 2+ and diacylglycerol (DAG) for their activation; the novel ones (δ, ε, η, and θ) are dependent on DAG but not Ca 2+ ; the atypical ones (ζ and λ/ι) are independent of both Ca 2+ and DAG [4-6]. Among them, PKCε is the only isoenzyme that has been considered as an oncogene which regulates cancer cell proliferation, migration, invasion, chemo-resistance, and differentiation via the cell signaling network by interacting with three major factors RhoA/C, Stat3, and Akt [9-13]. PKCε is overexpressed in many types of cancer, including bladder cancer [14], prostate cancer [15], breast cancer [16], head and neck squamous cell carcinoma [17], and lung cancer [18] as well as RCC cell lines [19,20].…”

Section: Introductionmentioning

confidence: 99%

The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma

Huang

Cao

et al. 2011

J Exp Clin Cancer Res

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Protein kinase C epsilon (PKCε), an oncogene overexpressed in several human cancers, is involved in cell proliferation, migration, invasion, and survival. However, its roles in clear cell renal cell carcinoma (RCC) are unclear. This study aimed to investigate the functions of PKCε in RCC, especially in clear cell RCC, to determine the possibility of using it as a therapeutic target. By immunohistochemistry, we found that the expression of PKCε was up-regulated in RCCs and was associated with tumor Fuhrman grade and T stage in clear cell RCCs. Clone formation, wound healing, and Borden assays showed that down-regulating PKCε by RNA interference resulted in inhibition of the growth, migration, and invasion of clear cell RCC cell line 769P and, more importantly, sensitized cells to chemotherapeutic drugs as indicated by enhanced activity of caspase-3 in PKCε siRNA-transfected cells. These results indicate that the overexpression of PKCε is associated with an aggressive phenotype of clear cell RCC and may be a potential therapeutic target for this disease.

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“…PKCepsilon has been extensively investigated for its role in cell proliferation and apoptosis, being recognized as an oncoprotein promoting tumorigenesis, cancer survival and invasiveness (8). Our publications pinpoint to PKCepsilon as relevant modulator of hematopoietic progenitors' differentiation pathways, since its over-expression has been linked to a significant impairment of MK differentiation up to a complete block of maturation, as described in acute myeloid leukemia blasts (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 88%

Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with disease severity and thrombotic risk

Masselli¹,

Carubbi²,

Pozzi³

et al. 2017

Ann. Transl. Med.

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Background: Myelofibrosis (MF) is the most aggressive Philadelphia-negative chronic myeloproliferative neoplasm (MPN) with high morbidity and mortality due to thrombo-hemorrhagic complications and leukemic transformation. MF is characterized by profound alterations of megakaryocytopoiesis, with consequent abnormalities in platelet number and function. We recently showed that the overexpression of the oncoprotein PKCepsilon plays a key role in the aberrant differentiation of MF megakaryocyte clone and that its levels correlate with disease burden. Moreover, our group previously demonstrated that PKCepsilon is over-expressed in platelets from patients with acute myocardial infarction (MI) and accounts for their increased reactivity. On these bases, we investigated here the activation state and PKCepsilon expression of MF platelets, testing potential correlations with thrombotic risk and disease aggressiveness.Methods: Platelets were isolated from peripheral blood samples of MF patients and healthy donors (HDs).Patients were stratified according to the IPSS/DIPSS risk category and history of cardiovascular events.Platelet activation was assessed by flow cytometry. PKCepsilon mRNA and protein levels were determined by real time-PCR and western blot.Results: MF platelets circulate in an activated status and display significantly higher levels of PKCepsilon compared to HDs. In MF patients, PKCepsilon platelet levels were associated with high-risk disease as well as with a positive history of major cardiovascular events.Conclusions: PKCepsilon is configuring as the common denominator of neoplastic transformation and thrombus formation in MF. Overall, our data pinpoint PKCepsilon as a potential novel biomarker of disease aggressiveness and thrombotic risk in this hematologic neoplasm.

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Protein kinase Cε as a cancer marker and target for anticancer therapy

Cited by 47 publications

References 89 publications

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma

Platelet expression of PKCepsilon oncoprotein in myelofibrosis is associated with disease severity and thrombotic risk

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