Transformation-specific decrease of phosphorylation of 80K protein, a substrate of protein kinase C, in NIH3T3 cells

Phosphorylation in normal and transformed NIH3T3 cells of the 80K protein, a specific substrate for protein kinase C, was compared by means of two-dimensional gel analysis. We obtained evidence that NIH3T3 cells transformed by the c-raf or H-ras oncogene maintained a decreased level of phosphorylation of the 80K protein, with or without phorbol ester (TPA)-stimulation, at all concentrations of serum tested while normal NIH3T3 cells maintained an elevated level of phosphorylation of the 80K protein. Furthermore, NIH3T3 cells transformed by N-ras, K-ras, src, mos or polyoma middle T antigen exhibited a decreased level of phosphorylation of the 80K protein. These events were confirmed by an analysis of a hormone-inducible H-ras transformant. Thus, phosphorylation of the 80K protein is inversely correlated with cellular transformation.     

Lung Cancer Cells Often Express High Levels of Protein Kinase C Activity

We analyzed protein kinase C (PKC) activity in twenty-two tumor cell lines derived from lung, pancreas, stomach, tongue and vulva, and found that lung cancer cells often (9 out of 13) exhibit significantly higher PKC activity than other types of cancer cells. The PKC in these lung cancer cells was separated into one major and one minor peaks by a Mono Q column chromatography. The PKC in the major peak had an absolute requirement for Ca^2±, phosphatidylserine and 12-O-tetradeca-noylphorbol-13-acetate (TPA), as expected. However, the PKC in the minor peak did not require TPA for its activation. Hydroxyapatite column chromatography revealed that the PKC in the major peak is type III. These results indicate that in lung cancer cells type III PKC activity is often elevated compared to other types of cancer cells. The growth of many lung cancer cell lines was inhibited by TPA.     

Activated Protein Kinase C Directly Phosphorylates the CD34 Antigen in Acute Lymphoblastic Leukemia Cells

The precursors of all blood cell lineages are contained within the 1-3% of bone marrow cells which express the CD34 antigen and this population can reconstitute the hematopoietic system of lethally irradiated animals and humans. A potential regulatory role for the CD34 antigen in progenitor cell function and differentiation was indicated by our recent findings that the CD34 antigen can be phosphorylated in vivo to high stoichiometry in primitive CD34 + cell-lines by activated protein kinase C. To exclude the possibility that these effects were restricted to cell-lines, we have performed similar experiments on fresh cells from a patient with drug-resistant acute lymphoblastic leukemia. Similar to our previous findings, we found the CD34 antigen to be hyperphosphorylated in lymphoblasts labeled in the presence of active phorbols. The same peptides which were hyperphosphorylated in phorbol-stimulated cell-lines were also phosphorylated in phorbol-stimulated lymphoblasts. These data indicate that CD34 is a substrate molecule for PKC in fresh CD34+ lymphoblasts and underline the role of modulators of PKC activity in the biology of primitive leucocytes.     

A Tyrosine-specific Protein Kinase Inhibitor, α-Cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide, Blocks the Phosphorylation of Tyrosine Kinase Substrate in Intact Cells

Inhibition by α-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide (ST 638) of tyrosine-specific protein kinase was examined using epidermal growth factor (EGF)-treated A431 cells at the concentration of 25 to 100 μ M . ST 638 had negligible effects on the growth and morphology of A431 cells and on EGF binding to its receptor, and subsequent down-regulation of the receptor. ST 638 specifically inhibited EGF-induced phosphorylation of tyrosine residues of whole cell proteins in a dose-dependent manner without affecting the phosphorylation of serine and threonine residues. ST 638 greatly inhibited the EGF-induced phosphorylation of lipocortin I at 25 μ M , and yet had a negligible effect on the EGF-induced phosphorylation of EGF receptor. Neither the amount of [³⁵S]methionine-labeled lipocortin I nor the serine/threonine phosphorylation level of fodrin β-subunit was affected by the same concentration of ST 638. These results indicate that the phosphorylation of lipocortin I is not relevant to the transformation of A431 cells. In cell lines transformed by src or fgr oncogene encoding tyrosine kinase, ST 638 also inhibited phosphorylation of calpactin I (p36) without affecting that of the oncogene products. Two-dimensional polyacrylamide gel electrophoresis showed that ST 638 specifically inhibited the EGF-induced phosphorylation and dephosphorylation of cellular proteins in A431 cells.     

Differentiation and Growth Modulation of Myeloid Leukemia Cells by the Protein Kinase C Activating Agent Bryostatin-1

Bryostatin-1 (Bryo), a macrocyclic lactone of the sea water bryozoan Bugula neritina, is a potent activator of protein kinase C and was found to exhibit antineoplastic activity in several systems. We studied the effect of Bryo on differentiation and growth modulation of human myeloid leukemia cell lines and freshly explanted blood cells from patients with myeloid leukemia. Alterations at the molecular level and phenotypic changes triggered by Bryo were similar, but not identical, to those induced by phorbol esters. Bryo was able to inhibit cellular proliferation as evidenced by [³H]-thymidine uptake and induced morphological changes associated with monocytic differentiation. In studies using continuous cell lines, the glucocorticoid dexamethasone was unable to prevent the Bryo-induced growth inhibition or the induced phenotypic changes. However, in fresh myeloid Blood cells dexamethasone attenuated these Bryo-triggered effects. Our own data taken together with reports from the literature reviewed here suggest the following conclusions: (i) Bryo, while lacking tumor promoting activity, is able to induce differentiation in maturation arrested leukemia cells; (ii) it exhibits selective antiproliferative properties in normal or malignant hematopoietic cells and supports growth of multipotent stem cells. These features might qualify Bryostatin-1 as a potential candidate for promising research and possibly for future clinical applications.     

蛋白激酶C与耐药性KB细胞的多药抗药性

目的 :研究蛋白激酶C(PKC)在肿瘤细胞多药抗药性的作用及机制。方法 :测定KB细胞及其耐药株的PKC活性及PKC调节剂对细胞药敏、药物代谢和耐药膜糖蛋白表达及其磷酸化的影响。结果 :耐药株胞质和胞膜的PKC活性分别是KB细胞的 6 6倍和 5 2倍 ,膜糖蛋白阳性率为 4 7 5 % ,明显高于KB细胞的 2 8% ;而且膜糖蛋白的磷酸化明显增强。耐药株对罗丹明 12 3的外排显著加快 ,蓄积明显减少。PKC激活剂佛波乙酯使耐药株的药物外排增加了 60 % ,蓄积减少了 70 % ;PKC抑制剂Stau rosprin使耐药株药物外排后潴留增加了 2 5倍 ,蓄积增加了 14倍 ,抗药性被逆转了 14倍 ,但未影响耐药膜糖蛋白的表达。结论 :PKC活性增高与耐药株抗药性密切相关 ;而且抗药性是通过膜糖蛋白磷酸化增强 ,增加药物外排 ,减少药物蓄积而实现的     

卵巢癌中PKC和P-gp 的表达及其临床意义

 目的 探讨卵巢癌组织蛋白激酶C(PKC)和P-糖蛋白(P-gp)表达及其临床意义。方法 用免疫组化S-P法检测35例卵巢癌、20例卵巢良性肿瘤和20例正常卵巢组织中PKC和P-gp的表达，并进行相关临床因素分析。结果 (1)PKC、P-gp在卵巢恶性肿瘤中的表达明显高于在良性及正常组织中的表达；初治和复发病例PKC阳性表达有显著差异(P<0．05)。(2)卵巢癌PKC的表达与临床病理因素无直接关系。(3)卵巢癌中PKC和P-gp的表达有显著相关性(P<0．05)。(4)化疗对PKC表达阳性和阴性卵巢癌患者的有效率分别为23．5％、66．7％(P<0．05)。(5)PKC表达阴性患者的预后优于阳性者(P=0．039)。结论 PKC表达与P—gp的表达明显相关，可能在卵巢癌多药耐药中起重要作用。     

Inhibition by Protein Kinase C Inhibitor of Expression of Leukocyte Function-associated Antigen-1 Molecules in Rat Hepatoma AH66F Cells

To examine the mechanism of inhibition by protein kinase C (PKC) inhibitors of the adhesion of highly malignant hepatoma AH66F cells to the mesentery-derived mesothelial cell (M-cell) layer through leukocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1, the effects of a PKC inhibitor, NA-382, on the expression of LFA-1 molecules in AH66F cells were examined and compared with those in thymocytes from normal rats. NA-382 inhibited the adhesion of AH66F cells to the M-cell layer and the expression of LFA-1 on the membrane of the hepatoma cells after treatment for more than 24 h. It was confirmed that AH66F cells express similar mRNAs for LFA-1 subunits to those of thymocytes, and their levels were also decreased after treatment with NA-382. On the other hand, the LFA-1-mediated adhesion and the expression of both protein and mRNA for LFA-1 subunits in thymocytes were not changed by the PKC inhibitor. These results suggest that the expression of LFA-1 molecules in AH66F cells may be regulated by PKC via quite different mechanisms from those in normal lymphocytes     

Protein Kinase C Inhibition by UCN-01 Induces Apoptosis in Human Glioma Cells in a Time-dependent Fashion

Recent studies in our laboratory have shown that UCN-01 (7-hydroxystaurosporine), which is a derivative of the non-selective protein kinase inhibitor staurosporine that exhibits relative selectivity for protein kinase C (PKC), is a potent inhibitor of glioma growth in in vitro and in vivo models. This agent exhibits both cytotoxic and cytostatic effects, depending on the time period of drug exposure. In the present study, we examined whether UCN-01-induced cytotoxicity correlated with the induction of apoptosis, and characterized further the time course of this process as a prelude to application of UCN-01 in clinical trials. We first demonstrated that the cytotoxic effects of UCN-01 were associated with the induction of morphological features of apoptosis. Secondly. we identified electrophoretic features of apoptosis semiquantitatively at a series of time points using field inversion gel electrophoresis. These studies showed a peak in the induction of high-molecular-weight DNA fragmentation after 3–6 days of drug treatment. Thirdly, we measured the percentage of cells undergoing apoptosis at various time points using a terminal transferase-catalyzed in situ end-labeling technique, which confirmed a time- and concentration-dependent increase in apoptotic cell numbers. This correlated with a progressive decrease in the percentage of cells that were viable as assessed by trypan blue exclusion. Cell killing peaked within 2–4 days after beginning UCN-01 treatment, but continued at a lower level in the ensuing days. Taken together, these studies demonstrated that extended periods of exposure to UCN-01 are needed for optimal manifestation of cytotoxic effects against glioma cells, a factor that must be taken into consideration in the design of future clinical trials with this agent for malignant gliomas.     

Inhibition of protein kinase C and proto-oncogene expression by crocetin in NIH/3T3 cells

Crocetin, a carotenoid isolated from the seeds of Gardenia jasminoides, was found to be a potent inhibitor of tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. When mouse fibroblast NIH/3T3 cells were treated with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction to the particulate fraction. Pretreatment with 60 and 120 μM crocetin for 15 min inhibited the TPA-induced PKC activity in the particulate fraction by 50% and 66%, respectively, but did not affect the level of PKC protein. Crocetin also reduced the level of TPA-stimulated phosphorylation of cellular proteins. Cells pre-treated with crocetin (120 μM) had 55% less PKC [³H]phorbol dibutyrate-binding capacity. Suppression of TPA (100 ng/mL)-induced c-jun and c-fos gene expression was also observed in the mouse fibroblast cells pre-treated with crocetin (30, 60, and 120 μM). Our results provided a basis for understanding the inhibitory effect of crocetin on TPA-mediated tumor promotion. © 1996 Wiley-Liss, Inc.     

Activation of Protein Kinase C by Mycobacterial Cord Factor, Trehalose 6-Monomycolate, Resulting in Tumor Necrosis Factor-α Release in Mouse Lung Tissues

Cord factors are mycoloyl glycolipids in cell walls of bacteria belonging to Actinomycetales , such as Mycobacterium , Nocardia and Rhodococcus . They induce granuloma formation in the lung and interstitial pneumonitis, associated with production of macrophage-derived cytokines. We studied how cord factors induce biological activities in the cells. Cord factors isolated from M. tuberculosis , trehalose 6-monomycolate (mTMM) and trehalose 6,6'-dimycolate (mTDM), enhanced protein kinase C (PKC) activation in the presence of phosphatidylserine (PtdSer), diacylglycerol and Ca²⁺, and mTMM activated PKCα more strongly than PKCβ or γ under the same assay conditions. Kinetic studies of mTMM in response to PKC activation revealed that mTMM increased the apparent affinity of PKC to Ca²⁺ in the presence of both PtdSer and diolein. Although this is similar to observations with unsaturated fatty acids, such as arachidonic acid, mTMM was synergistic with PtdSer for PKC activation, but arachidonic acid was not. mTMM was also different as regards PKC activation, as phorbol ester was. A single i.p. administration of mTMM to mouse induced tumor necrosis factor-α (TNF-α) in serum and in the lung, which is a unique target tissue of cord factors. Based on our recent finding that TNF-α is an endogenous tumor promoter, the correlation between lung cancer and pulmonary tuberculosis is discussed.     

Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma Management

The Protein kinase CK2 (formerly known as casein kinase 2) is a highly conserved serine/ threonine kinaseoverexpressed in various human carcinomas and its high expression often correlates with poor prognosis. CK2 proteinis localized in the nucleus of many tumor cells and correlates with clinical features in many cases. Increased expressionof CK2 in mice results in the development of various types of carcinomas (both solids and blood related tumors, suchas (breast carcinoma, lymphoma, etc), which reveals its carcinogenic properties. CK2 plays essential roles in many keybiological processes related to carcinoma, including cell apoptosis, DNA damage responses and cell cycle regulation.CK2 has become a potential anti-carcinoma target. Various CK2 inhibitors have been developed with anti-neoplasticproperties against a variety of carcinomas. Some CK2 inhibitors have showed good results in in vitro and pre-clinicalmodels, and have even entered in clinical trials. This article will review effects of CK2 and its inhibitors on commoncarcinomas in in vitro and pre-clinical studies.     

PKC激活剂佛波酯PMA和抑制剂Staurosporine对大肠癌HT-29细胞黏附作用的影响

目的　探讨蛋白激酶C(PKC )激活剂佛波酯PMA和PKC抑制剂Staurosporine(SP)对大肠癌HT -2 9细胞黏附作用的影响。方法　采用体外细胞培养观察、细胞黏附人脐带静脉内皮细胞(HUVECs)测定、Westernblot分析黏附分子E Cadherin(E Cad)、LamininReceptor(LnR)、αCatenin和αCatenin表达等方法,研究PMA和SP对HT- 2 9细胞黏附作用的影响。结果　从体外细胞培养观察和黏附HUVECs实验结果发现,10 0nmol/LPMA处理后,和培养液对照组相比可见HT- 2 9细胞由圆形变成成纤维细胞样生长,细胞发生游走、扩散,HT -2 9细胞间黏附减弱,而对HUVECs的黏附增强(P <0 .0 5 )。而10 0nmol/LPMA和10 0nmol/LSP联合处理HT 2 9细胞,可见细胞成片生长,HT- 2 9细胞间黏附增强,而对HUVECs的黏附则降低(P <0 .0 5 )。Westernblot分析结果提示,培养液对照组细胞可较高水平表达E Cad、LnR ,而低水平表达αCatenin、αCatenin。10 0nmol/LPMA作用细胞可诱导HT- 2 9细胞LnR表达水平增强,而E Cad表达水平轻度减弱,对αCatenin、α- Catenin表达水平无作用。而SP可拮抗PMA的作用,使LnR表达水平降低,E Cad表达水平增强,而对α- Catenin和α- Catenin的表达亦无影响。结论　PKC激活剂佛波酯PMA可促使肿瘤细胞间的同质性黏附能力减弱,与HUVECs间     

Critical Role of Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Novel Vitamin K Analog-induced Cell Death

In the present study, we show that 2-(2-hydroxyethylsulfaryl)-3-methyl-1,4-naphthoquinone, or CPD 5, is a potent growth inhibitor for pancreas cancer cell lines (ID₅₀: 21.4±3.8, 31.8±2.7 and 55.2±4.5 μ M for MiaPaCa, Panc-1 and BxPc3, respectively). It induced protein tyrosine phosphorylation of hepatocyte growth factor (HGF) receptor (c-Met) or epidermal growth factor receptor (EGFR), which increased progressively to a maximum level at 30 min in Panc-1 cells. The receptor phosphorylation by CPD 5 was indicated to be functional, since these receptors were found to bind with Grb2 or SOS1 protein. CPD 5 was also suggested to induce phosphorylation of external signal-regulated kinase (ERK). EGF induced cell proliferation through ERK phosphorylation, since U0126, which is an inhibitor of ERK phosphorylation, abrogated the increase of cyclin D1 by EGF. HGF increased the amount of p27 protein, suggesting that it is associated with cell differentiation. By contrast, U0126 reduced CPD 5-induced cell death. On two-dimensional electrophoresis, we found an extra type of phospho-ERK, and this was completely and selectively abolished by U0126. These results suggest that ERK phosphorylation, especially the extra spot on two-dimensional gel, is critically associated with CPD 5-mediated cell death.     

大肠癌细胞侵袭转移的PKC调节机制研究

目的　探讨蛋白激酶C(PKC)对大肠癌细胞侵袭转移的调节机制。方法　采用羊膜侵袭培养系统和明胶酶谱分析的方法 ,研究PKC激活剂佛波酯PMA ,对人大肠癌细胞株HT 2 9体外侵袭作用的影响及PKC抑制剂staurosporine(SP)对PMA的拮抗作用 ,研究这种体外的侵袭作用与细胞分泌 72kD的基质金属蛋白酶MMP 2和 92kD的基质金属蛋白酶MMP 9的关系。结果　PMA可显著增强HT 2 9细胞的侵袭性 ,与对照组相比 ,有显著性差异 (P <0 .0 1) ,而SP则可拮抗PMA的这种诱导作用。PMA还可增加HT 2 9细胞分泌MMP 2和MMP 9,而SP则可拮抗PMA的这种诱导作用 ,抑制MMP 2和MMP 9的分泌。结论　PKC可调节大肠癌细胞侵袭转移 ,PKC的激活可诱导大肠癌细胞侵袭性增强和增加MMP 2和MMP 9的分泌 ,PKC的抑制可促进大肠癌细胞侵袭性降低和减少MMP 2和MMP 9的分泌。MMP 2和MMP 9的分泌与肿瘤细胞侵袭性有密切关系 ,PKC可能通过调节MMP 2、MMP 9的分泌来影响肿瘤细胞侵袭和转移特性的     

Inhibition by Sphingosine of Leukemic Cell Killing by Human Monocytes Activated with Interleukin-2: A Possible Role of Protein Kinase C

Sphingosine and its analogs, which inhibit protein kinase C (PKC), are known to be potent inducers of apoptosis in tumor cells. However, we were concerned that sphingosine might also interfere with anti-tumor cells of the immune system. Therefore, we evaluated the effect of sphingosine on activation of human monocytes by interleukin-2 (IL-2) for killing of leukemic cells. Monocytes, purified by elutriation and adherence, were activated with IL-2 or interferon-gamma (IFN-γ) in the presence or absence of sphingosine or another inhibitor for 18 h. Then the monocytes were washed and the culture medium was replaced with fresh medium to remove the sphingosine. HL-60 and K562 leukemic cells were added to the monocyte cultures. Over the next 48 h, the cytotoxic activity of the monocytes towards the leukemic cells was assessed by means of an ¹¹¹indium-releasing assay. IL-2-activated monocytes lysed 48±3% of HL-60 cells and 44±3% of K562 cells. Sphingosine, dihydrosphingosine, N, N-dimethylsphingosine, and the PKC inhibitor H7 inhibited the activation of monocytes by IL-2, blocking cytotoxic activity against the leukemic cells by approximately 75%. These inhibitors were not toxic to monocytes at the concentrations used. In a PKC assay, sphingosine and H7 inhibited PKC activity in IL-2-treated monocytes. Thus, sphingosines, by inhibiting PKC activity, inhibited activation of monocytes by IL-2, which inhibited the killing of leukemic cells.     

实验性肺癌中蛋白激酶C的表达及意义

[目的]建立肺癌动物模型基础上研究蛋白激酶C(PKC)α在肺鳞癌组织中表达,探讨其在肺鳞癌发生发展中的可能作用.[方法]用肺叶支气管内灌注致癌物碘油溶液诱发大白鼠肺癌的方法建立大鼠肺鳞癌模型,以免疫组化方法研究PKCα在肿瘤组织、肿瘤周围组织及正常组织的表达.[结果]诱发的肺部肿瘤均为肺鳞癌,诱癌率达77.8%;肺鳞癌组织中PKCα表达明显增高,在诱癌组对侧肺组织表达也明显高于正常肺组织,分别为(24.08±2.93)%,(5.00±2.10)%,(1.96±0.29)%,差异有显著性(P＜0.05).[结论]肺癌组织中PKCα的异常高表达提示致癌剂可能通过活化PKCα介导的多个环节的信号转导而参与了肺鳞癌的发生、发展.     

Anticancer Drug-mediated Induction of Multidrug Resistance-associated Genes and Protein Kinase C Isozymes in the T-Lymphoblastoid Cell Line CCRF-CEM and in Blasts from Patients with Acute Lymphoblastic Leukemias

The major determinants mediating drug resistance in acute lymphoblastic leukemias (ALL) unresponsive to chemotherapy, are still unclear. For example, it is still unknown whether selection or induction processes are responsible for drug resistance here or whether protein kinase C (PKC) isozymes contribute to the resistant phenotype. Therefore, inducibility of resistance factors or PKC isozymes genes was examined in CCRF‐CEM cells treated with diverse anticancer drugs‐ adriamycin, camptothecin, etoposide or vincristine‐at sublethal concentrations for 24 h. MDR1, MRP1, LRP and PKC isozyme α, β₁, β₂, ε, ι, η, θ, ζ gene expression was determined by cDNA‐PCR. We found significant dose‐dependent, mostly combined, induction of the MDR1, MRP1 and LRP genes. Significantly enhanced gene expression of the majority of PKC isozyme genes was found after treatment with camptothecin. PKCζ was upregulated throughout by each anticancer drug applied in this setting. A series of selected CCRF‐CEM‐derived multidrug resistance (MDR) sublines also showed enhanced expression of the PKC isozymes compared to the parental cell line. MDR1 and PKCη gene expression levels were correlated highly significantly. Blasts from two patients with ALL during the first week of monotherapy with steroids revealed combined induction of the MDR1, multidrug resistance‐associated protein 1 (MRP1), lung cancer resistance‐related protein (LRP) and most PKC isozymes, predominantly PKCζ. Another patient with T‐ALL, who failed to respond to four months of intensive chemotherapy, showed an enhanced MRP1 gene expression combined with markedly overexpression of PKCη and PKCθ. Furthermore, the camptothecin and etoposide‐mediated induction of resistance factors in the CCRF‐CEM cell line could be suppressed by staurosporine, a rather unspecific inhibitor of protein kinases. However, selective inhibitors of PKC isozymes (bisindolylmaleimide GÖ 6850, indolocarbazole GÖ 6976) produced no significant effects here. Therefore, the PKC isozymes η, θ and ζ are of interest as potential targets to overcome drug resistance in ALL.     

蛋白激酶C与K562/A02细胞多药耐药相关性的研究

目的 探讨蛋白激酶C(protein kinase C，PKC)在K562／A02细胞多药耐药的产生及其逆转中的作用。方法 用放射免疫法检测了耐药细胞株K562／A02及其敏感株K562的静息PKC活性水平，并观察了柔红霉素(daunomycin，DNR)以及耐药调节剂粉防己碱(tetrandrine．Tet)、屈洛昔芬(droloxifene，Drol)单独或联合应用后细胞PKC活性的变化。结果 静息状态下耐药细胞株K562／A02的PKC活性显著高于敏感株K362，有效调节浓度的Tet、Drol单独作用于K562、K562／A02细胞均可显著下调其PKC活性，联合应用有显著协同性。1μg／mLDNR可显著下调K562细胞的PKC活性，部分下调K562／A02细胞的PKC活性，有效调节浓度的Tet、Drol单独或联合应用均可加强其作用。结论 PKC参与K562／A02细胞多药耐药(multidrug resistance,MDR)的形成，Tet、Drol逆转K562／A02细胞的MDR可能与下调其PKC活性有关。     

甘油二酯激酶α、蛋白激酶C在肝癌组织中的表达及临床意义

 目的 研究肝癌组织中甘油二酯激酶α (Diacylglycerol Kinase α, DGKα)和蛋白激酶C（PKC）的表达及临床意义。方法 应用免疫组化检测DGKα在60例肝癌、癌周组织及10例正常肝组织中的表达,统计分析DGKα的表达与临床病理因素的关系。 结果 DGKα和PKC蛋白在正常肝组织、癌周组织和肝癌组织的阳性表达率逐渐降低,但在肝细胞的表达部位却逐渐从胞浆移至胞膜。DGKα阳性表达率的差异与原发性肝癌的分化类型、是否有门静脉癌栓和TNM分期有统计学意义(P <0.05)。结论 在越晚期、分化越差的肝癌中DGKα的活性越强,DGKα促进了原发性肝癌的病理进程。