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Z Yan

Publications and source records attributed to Z Yan.

At least 145 records · Page 8Linked to original sources
PubMed1998

Cellular cholesterol storage in the Niemann-Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D.

Apolipoprotein D (apoD), a member of the lipocalin superfamily of ligand transporters, has been implicated in the transport of several small hydrophobic molecules including sterols and steroid hormones. We have previously established that apoD is a secreted protein from cultured mouse astrocytes and that treatment with the oxysterol 25-hydroxycholesterol markedly stimulates apoD release. Here, we have investigated expression and cellular processing of apoD in the Niemann-Pick type C (NPC) mouse, an animal model of human NPC, which is a genetic disorder affecting cellular cholesterol transport. NPC is phenotypically characterized by symptoms of chronic progressive neurodegeneration. ApoD gene expression was up-regulated in cultured NPC astrocytes and in NPC brain. ApoD protein levels were also increased in NPC brain with up to 30-fold higher apoD content in the NPC cerebellum compared with control mice. Subcellular fractionation of NPC brain homogenates revealed that most of the apoD was associated with the myelin fraction. ApoD was found to be a secreted protein from cultured normal astrocytes and treatment with the oxysterol, 25-hydroxycholesterol, markedly stimulated apoD release (by five- to 10-fold). By contrast, secretion of apoD from NPC astrocytes was markedly reduced and could not be stimulated by oxysterol treatment. Secretion of apoE, another apolipoprotein normally produced by astrocytes, was similar in NPC and control cells. Furthermore, apoE secretion was not potentiated by oxysterol treatment in either cell type. Plasma levels of apoD were sixfold higher in NPC, whereas hepatic levels were substantially reduced compared with controls, possibly reflecting reduced hepatic clearance of the circulating protein. These results reveal hitherto unrecognized defects in apoD metabolism in NPC that appear to be linked to the known defects in cholesterol homeostasis in this disorder.

Animals↗
PubMed1998

Adenovirus colitis in human immunodeficiency virus infection: an underdiagnosed entity.

Adenovirus infection of the gastrointestinal tract in human immunodeficiency virus (HIV)-infected patients is rarely reported, probably because of a lack of familiarity of most pathologists with diagnostic criteria during routine light microscopy and possible misidentification as cytomegalovirus infection. We studied colonoscopic biopsy specimens from 135 HIV-infected patients with clinically suspected cytomegalovirus colitis during a 4.5-year period to morphologically identify the presence of adenovirus infection. Immunohistochemical staining for adenovirus was performed for confirmation on all suspected cases. Adenovirus infected cells showed characteristic amphophilic or eosinophilic nuclear inclusions, predominantly affecting the surface epithelium and characteristically involving goblet cells. Sixteen cases showed morphologic features of adenovirus infection, all confirmed by immunohistochemistry. Twelve cases also showed cytomegalovirus infection, whereas 4 showed adenovirus alone. In 10 cases, adenovirus colitis was not recognized during initial routine histopathologic diagnostic evaluation. Adenovirus inclusions also were discovered in the stomach, the duodenum, and the liver in single cases. Conclusions are as follows: (1) Adenovirus colitis has been underdiagnosed at our institution and, we suspect, in general. (2) The morphologic features and nuclear inclusions of adenovirus colitis are characteristic and can be identified reliably by routine light microscopy. (3) Adenovirus infection also may be diagnosed morphologically in extracolonic sites, such as the stomach, the small intestine, and the liver. (4) Coinfection of adenovirus with cytomegalovirus and other agents is seen frequently, but, less frequently, adenovirus may be identified as a sole pathogen.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Cytochrome c promoter activity in soleus and white vastus lateralis muscles in rats.

Cytochrome c protein and mRNA are 300 and 100% higher, respectively, in the soleus muscle (predominantly slow-twitch oxidative) than the white vastus lateralis (predominately fast-twitch glycolytic) muscle (W. W. Winder, K. M. Baldwin, and J. O. Holloszy. Eur. J. Biochem. 47: 461-467, 1974; M. M. Lai and F. W. Booth. J. Appl. Physiol. 69: 843-848, 1990). However, the mechanisms controlling these differences in cytochrome c mRNA are largely unknown. The present study employed direct plasmid injection techniques to determine whether the proximal promoter (-726 to +610) of the rat somatic cytochrome c gene was more active in the soleus than in white vastus lateralis muscles in rats. No difference between the soleus and white vastus lateralis muscles for the activities of the -726, -631, -489, -326, -215, -159 and -149 cytochrome c promoters was noted. The results of this study suggest that additional elements (outside of -726 to +610) in the cytochrome c gene may be required, or posttranscriptional regulation may account, for the higher cytochrome c mRNA in the slow-twitch oxidative muscle.

Animals↗
PubMed1998

Clinical pharmacology and toxicology of dichloroacetate.

Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses.

Animals↗
PubMed1998

Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) production by luteinized human granulosa cells in vitro; a paracrine signal in corpus luteum formation.

Vascularization is a prerequisite for corpus luteum formation. Angiogenesis is thought to be regulated by vascular growth factors. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) specifically induces endothelial cell proliferation as well as angiogenesis and increases capillary permeability. Recently, VEGF/VPF-mRNA expression was demonstrated in luteinized human granulosa cells (GC) in vitro. In addition, the production of VEGF/VPF by human granulosa can be demonstrated immunocytochemically. VEGF/VPF is thought to mediate its effects through specific cell surface receptors. So far, two VEGF/VPF-receptors (VEGF/VPF-R) have been identified (KDR, and flt-1). A third receptor (flt-4) is highly correlated to KDR and flt-1, but the true ligand for this receptor is still unknown. The appearance of all three receptors is more or less restricted to endothelial cells. To clarify whether VEGF/VPF acts in an auto- or paracrine fashion in human luteinized GC, mRNA was scrutinized for specific expression of the three receptors by Northern blot technique. No specific VEGF/VPF-R or flt-4 transcripts were detectable, indicating that VEGF/VPF is a genuine paracrine growth factor from human luteinized GC directed to endothelial cells.

Adult↗
PubMed1998

[Nucleotide sequence analysis of a species specific probe by an inserted fragment from recombinant plasmid pCX7 of L. interrogans sensu stricto serovar lai].

The etiological agents of leptospirosis are the pathogenic leptospires (L. interrogans sensu lato) which can be divided into 223 serovars organized into 23 serogroups. The serovar remains the basic taxon, but serotyping may now be accomplished and recognized by acceptable methods. Complementary molecular approaches are being used extensively to assess genetic relatedness amongst leptospires with restriction endonuclese analysis (REA), pulse field gel electrophoresis (PFGE) and DNA-DNA hybridization as well established tools. However, the method is cumbersome and unsuitable for routine application. To develop a sensitive and specific method for identification of pathogenic leptospires, a genomic library of L. interrogans sensu stricto serovar lai was constructed with the plasmid vector pUC9. A recombinant plasmid, designated pCX7 which has homologous fragment of pathogenic leptospires was screened from the bank. pCX7 could recognize pathogenic leptospiral DNA fragment 1.7 kb of strain 017 without cross hybridization to nonpathogenic leptospiral DNA. Inserted fragment of pCX7 DNA sequencing was performed by Dr. Yan Zhengxin (Max-Plank-Institut fur Biology, Tubingen, Germany). Insert fragment was cloned into pBluescript and sequenced by using ABI(Applied Bio. Systems, Model 373A). Nucleotide sequences were analyzed by Dr. Xiao Jianguo (Texas University Medical School and School of Public Health, Center for Infectious Diseases) using a suit of computer program (NIH). One open reading frame of 306 nucleotids were identified. There were identifiable initiation codons, terminators, pribnow box and sextama box within the sequenced regions. These results further confirmed that the little homology between L. interrogans sensu strito and L. borgpeterseni serovar javanica, L. inadai serovar ranarun and serovar manhao (L. genomospecies 2), L. biflexa serovar patoc, L. illini. pCX7 DNA probe could provide a base for identification and classification of leptospires.

DNA, Bacterial↗
PubMed1998

[Detection of human telomerase activity by telomerase TRAP-ELISA assay].

OBJECTIVE: Telomeric repeat amplification protocol (TRAP) is now a conventional assay for detecting telomerase activity. However, this method presents problems owing to tedious quantification, radioisotopic handling and limited number of samples that can be examined each time. In order to alleviate these inconveniences, a novel telomerase TRAP-ELISA assay for human telomerase activity was developed. METHODS: Telomerase TRAP-ELISA assay is a system based on the combination of PCR-ELISA with TRAP. It was used to detect telomerase activity in 293 cells and RNase-pretreated or heat-treated cells as control. RESULTS: Telomerase activity assayed by TRAP-ELISA was positive when the number of 293 cells examined was 10, 10(2), 10(3), and 10(4). The A(formerly called OD) value depended on the number of 293 cells used in the assay. Telomerase activity of RNase-pretreated or heat-treated cells, and human normal endothelial cell was negative. The result of telomerase TRAP-ELISA was available within one day and was handled without radioisotope. CONCLUSION: Telomerase TRAP-ELISA assay is a non-radioisotopic, fast and quantitative method for detecting human telomerase activity.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

[Childhood rhadomyosarcoma in head and neck].

2 cases childhood rhadomyosarcoma in head and neck were reported, both patients were treated by surgery, radiotherapy or chemotherapy. The pathologic type, clinical stage, diagnosis, treatment and prognosis of the childhood rhadomyosarcoma were discussed.

Child↗
PubMed1998

[Antigen-induced airway leakage in asthmatic guinea-pigs and the effects of BRL 55834].

OBJECTIVE: To understand the role of airway leakage in asthma attack and investigate the effects of BRL 55834 on prophylaxis and treatment of asthma. METHOD: Ten normal and seventeen sensitized guinea-pigs were divided into 5 groups. After being anesthetized, right carotid artery, right jugular vein and trachea were cannulated to monitor systemic blood pressure, inject drugs, mechanical ventilate and record airway insufflation pressure (AIP). All animals were pretreated with atropine and propranolol (1 mg/kg) 30 min before experiment. DMSO or BRL 55834 was administered intravenously 2 min before intravenous injection of evans blue (EB, 30 mg/kg), Ovalbumin (OA, 3 mg/ml) was inhaled using an ultrasonic nebulier for 30 seconds 1 min after injection of EB. RESULT: (1) BRL 55834 (8 micrograms/kg) did not inhibit airway leakage in normal guinea-pig; (2) Airway leakage increased in sensitized guinea-pigs significantly after inhaling OA, 87 +/- 19 ng dye/mg tissue vs 53 +/- 7 ng dye/mg tissue in trachea (Tr); 119 +/- 67 ng dye/mg tissue vs 79 +/- 46 ng dye/mg tissue in main bronchus (MB); 65 +/- 44 ng dye/mg tissue vs 46 +/- 17 ng dye/mg tissue in central pulmonary airway (CiPA) and 50 +/- 31 ng dye/mg tissue vs 32 +/- 4 ng dye/mg tissue in peripheral pulmonary airway (PiPA, P < 0.05). (3) BRL 55834 inhibited airway leakage contrast to DMSO, especially in CiPA and PiPA, with an inhibition of 48% (Tr, P < 0.05), 57% (MB, P < 0.01), 44% (CiPA, P < 0.05), and 46% (PiPA, P < 0.05) after injection of BRL 55834 8 micrograms/kg, and 46% (Tr, P < 0.05), 57% (MB, P < 0.01), 56%(CiPA, P < 0.01) and 55% (PiPA, P < 0.01) after injection of BRL 55834 16 micrograms/kg, respectively. (4) BRL 55834 decreased base AIP in all groups, and inhibited OA-induced AIP increasing in sensitized guinea-pigs, with an inhibition of 49% (BRL 55834 8 micrograms/kg) and 57% (BRL 55834 16 micrograms/kg) in contrast to DMSO. BRL 55834 had a little side-effect on cardiovascular system, but without statistical significance. CONCLUSION: Airway leakage is one of the most important components in asthma attack, BRL 55834, a selective potassium channel activator, not only decreases airway leakage, but also inhibits OA-induced increase in airway resistance. All these are beneficial to prophylaxis and treatment of asthma.

Airway Resistance↗
PubMed1998

[Gas chromatographic determination of camphora, mentholum, isoborneol and borneol in Guanxingao].

Guanxingao is a kind of traditional Chinese rubber electuary medicine which is able to either cure or guard against coronary heart disease and angina pectoris. The contents of camphora, mentholum, isoborneol and borneol in Guanxingao are determined by gas chromatography. The purpose of the study is to detect and control the loss of the four volatile components through production and standing and to guarantee the curative effect. Chromatographic analysis was performed on a GC-4004 gas chromatograph(FID). The column was a 3 mm i.d. x 2 m stainless steel tube packed with 7% PEG-1500 on 100-110 mesh 102 non-silanized white support. The column and the FID temperatures were 115 degrees C and 180 degrees C respectively. H2 was the carrier gas, 30 mL/min. Internal standard method was used for the quantitative estimation with naphthalene as the internal standard. The linear ranges were at least within 50-450 mg/L (r = 0.9999, n = 4). The correction factors against naphthalene were 1.262-1.286 and the RSDs were 0.32%-1.5%(n = 12). The recoveries were 98.44%-101.9%. In comparison with the theoretical contents, the average loss percentages are 71.72% (camphora), 65.60% (mentholum) and 66.31% (isoborneol + borneol). The samples were pretreated by means of isothermal (35 degrees C) water-bath extraction with acetone for 6 times with four hours each.

Camphanes↗
PubMed1998

[Purification and characterization of cyclomaltodextrin glucanotransferase from alkaliphilic bacteria].

A cyclomaltodextrin glucanotransferase from alkaliphilic bacteria was purified to PAGE homogenous by ammonium sulfate precipitation and DEAE-cellulose DE-52 chromatography with 11.5 fold purification and 5.7% recovery. Mr estimated with concentration gradient PAGE was 151,000. The optimum conditions for activity were pH 7.0, temperature 60 degrees C, stable in the range 6.0-9.0 and below 50 degrees C. The enzyme activity was activated by salicin and maltitol, slightly inhibited by Sn2+, Mn2+, inositol and pullulan, strongly inhibited by Ag+, Cu2+, Al3+, Fe2+, Pb2+, Hg2+ and Zn2+. The maximum absorption was at 270 nm in ultraviolet spectrum, the maximum emission wavelenghth in the excitation spectrum was 283 nm, the maximum emission spectrum determined at 283 nm was 335 nm. The effects of some protein modification reagents on the CGTase activity have been studied. Histidine and tryptophan residues may be essential for activity, carboxyl groups might have some effects on the activity.

Bacteria↗
PubMed1998

Differential expression of cyclin-dependent kinase 6 in cortical thymocytes and T-cell lymphoblastic lymphoma/leukemia.

Cyclin-dependent kinase-6 (CDK6) is the earliest inducible member of the CDK family in human T lymphocytes, involved in growth factor stimulation and cell cycle progression. CDK6 is one of the targets of p16 and p15, CDK inhibitors encoded by MTS1 and MTS2, two tumor suppressor genes that are frequently deleted in T-cell leukemia. In this study we have investigated CDK6 expression in normal and neoplastic lymphoid tissues using immunohistochemistry and flow cytometry. In normal (six samples) and hyperplastic (four samples) thymuses, strong CDK6 expression was observed in a discrete proportion of cortical thymocytes (10 to 15%), mainly located in the peripheral (subcapsular) zone of the cortex. All tested cases of T-cell lymphoblastic lymphoma/leukemia (T-LBL/ALL) showed strong CDK6 expression in the majority (up to 100%) of neoplastic lymphoid cells. Western blot analysis confirmed the expected CDK6 protein size (40 kd). According to Southern blot analysis, CDK6 overexpression in neoplastic T lymphoblasts was not due to gene amplification. In all other lymphomas investigated (28 peripheral T-cell non-Hodgkin's lympohomas (T-NHLs), 7 CD30+ anaplastic NHLs, 22 high-grade B-NHLs, 15 low-grade B-NHLs, 25 B-cell precursor ALLs), CDK6 was not expressed or expressed at low levels, with the only exception of three nasal angiocentric T-NHLs, all exhibiting CDK6 immunoreactivity comparable to that observed in T-LBL/ALL. These data provide evidence that CDK6 is abnormally expressed in T-LBL/ALL and may be involved in the pathogenesis of this malignancy. In addition, the quantitative difference of CDK6 expression between neoplastic and non-neoplastic cortical thymocytes can be potentially useful in the differential diagnosis of thymic neoplasms on histological and cytological specimens.

Blotting, Southern↗
PubMed1998

Pharmacokinetics and metabolism of [14C]dichloroacetate in male Sprague-Dawley rats. Identification of glycine conjugates, including hippurate, as urinary metabolites of dichloroacetate.

Pathways of metabolism of dichloroacetate (DCA), an investigational drug for the treatment of lactic acidosis in humans and a rodent hepatocarcinogen, are poorly understood. In this study, rats were given, by gavage, one or two 50 mg/kg doses of NaDCA. DCA labeled with 14C (carboxy carbon) or 13C (both carbons) was used in studies of disposition and pharmacokinetics, respectively. The effect of fasting for 14 hr before dosing was studied. Expired air, urine, feces, and tissues were collected from [14C]DCA-dosed rats. Urine was analyzed by HPLC, GC/MS, and NMR spectroscopy. Plasma samples were analyzed by GC/MS. DCA plasma elimination half-lives were 0.1 +/- 0.02 and 5.4 +/- 0.8 hr in young adult rats (180-265 g, 3-4 months of age) given one or two doses of DCA, respectively, and 9.7 +/- 1 hr in large, 16-month-old rats given two DCA doses. The percentage of the DCA dose excreted as CO2 varied from 17 to 46% and was lower (p < 0.001) in fed rats, compared with rats fasted overnight before dosing. Urine contained DCA and DCA metabolites, including oxalate, glyoxylate, and conjugated glycine (mainly hippurate and phenylacetylglycine). More unchanged DCA was excreted by large rats pretreated with DCA (mean, 20.2% of the dose) than by young adult rats given one dose of DCA (mean, 0.5%). This study confirmed that CO2, glycine, and oxalate are major products of DCA metabolism, it demonstrated that one dose of DCA altered the elimination of a subsequent dose, and it showed that age or body size, as well as access to food, significantly affected DCA metabolism in rats.

Animals↗
PubMed1997

Determination of dichloroacetate and its metabolites in human plasma by gas chromatography-mass spectrometry.

Sodium dichloroacetate (DCA) is an investigational drug for the treatment of lactic acidosis, and is also a putative environmental toxicant. We developed and validated a gas chromatography-mass spectrometry (GC-MS) technique that simultaneously measures lactate, DCA and its metabolites, monochloroacetate (MCA), glyoxylate, glycolate and oxalate in human plasma. Following administration of [13C1,2]DCA to healthy volunteers, blood samples were collected at various time points and the drug and its metabolites present in plasma were derivatized to their methyl esters by reacting with 12% boron trifluoride-methanol complex. The methyl esters were extracted with methylene chloride and analyzed by GC-MS. The quantitation limits of DCA and metabolites ranged between 0.3 and 1.5 microM. The coefficients of variation of the standards within the entire calibration range were between 0.3 and 14.5%. The bias values ranged between -16.3% and 18.7%. Total recoveries from derivatization and extraction were between 46.9% and 78.5%. The coefficients (r2) of linear regression of the calibration curves were 0.9882 to 0.9996.

Administration, Oral↗
PubMed1997

Oncogenic Ki-ras but not oncogenic Ha-ras blocks integrin beta1-chain maturation in colon epithelial cells.

Human colorectal tumors commonly contain mutations in Ki-ras but rarely, if ever, in Ha-ras. The selectivity for Ki-ras mutations in this tumor was explored using the HD6-4 colon epithelial cell line which contains no ras mutations. After adhesion to an extracellular matrix, HD6-4 cells polarize into columnar goblet cells with distinct apical and basal regions. Stable HD6-4 transfectants were made with mini-gene constructs of the oncogenic cellular Ki-ras4BG12V gene, the oncogenic Ha-rasG12V gene, or mini-gene constructs of wild-type Ki-ras4B as a control. Ki-ras mutations, but not Ha-ras mutations, disrupted colon epithelial cell apicobasal polarity and adhesion to collagen I and laminin. Three Ha-ras transfectants and three Ki-ras transfectants exhibited Ras proteins expressing the Val-12 mutation by Western blotting with pan-rasG12V antibody. Only wild-type Ki-ras transfectant cells and oncogenic Ha-ras transfectant cells synthesized the mature, fully glycosylated forms of beta1 integrin. Instead of the mature integrin beta1-chain, a faster migrating beta1-chain intermediate was detected on the cell surface and in the cytoplasm of the oncogenic Ki-ras transfectants. Expression of the oncogenic Ki-ras gene caused the altered beta1 integrin maturation because phosphorothiolated antisense oligonucleotides to Ki-ras reduced expression of both the mutant Ki-Ras protein and the aberrant integrin beta1-chain and increased expression of the mature integrin beta1-chain. Altered glycosylation generated the new beta1 integrin form since integrin core beta1-chain proteins of the same molecular weight were yielded in Ki-ras, Ha-ras, and control transfectants after removal of sugar residues with endoglycosidase F or following tunicamycin treatment to inhibit glycosylation. The selective effect of oncogenic Ki-ras on beta1 integrin glycosylation was not due to selective activation of mitogen-activated protein kinases because both mutated Ki- and Ha-ras genes activated this pathway and increased cell proliferation. Since blocking the glycosylation of integrin beta1-chain inhibited the adherence, polarization, and subsequent differentiation of colon epithelial cells, the selective effects of the oncogenic cellular Ki-ras gene on integrin beta1-chain glycosylation may account, at least in part, for the selection of Ki-ras mutations in human colon tumors.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Oncogenic c-Ki-ras but not oncogenic c-Ha-ras up-regulates CEA expression and disrupts basolateral polarity in colon epithelial cells.

Colon carcinomas commonly contain mutations in Ki-ras4B, but very rarely in Ha-ras, suggesting that different Ras isoforms may have distinct functions in colon epithelial cell biology. In an earlier study we had demonstrated that oncogenic Ki-ras4BVal-12, but not oncogenic Ha-rasVal-12, blocks the apicobasal polarization of colon epithelial cells by preventing normal glycosylation of the integrin beta1 chain of the collagen receptor. As a result, only the Ki-ras mutated cells exhibited altered cell to substratum attachment, whereas mutation of either Ras isoform activated mitogen-activated protein kinases. We have now asked whether intercellular adhesion proteins implicated in establishing basolateral polarity in colon epithelial cells are modulated by oncogenic Ki-Ras4BVal-12 proteins but not oncogenic Ha-RasVal-12 proteins. The embryonic adhesion protein carcinoembryonic antigen (CEA) was up-regulated on the mRNA and protein levels in each of three stable Ki-rasVal-12 transfectant lines but in none of three stable Ha-rasVal-12 transfectant lines. The elevated protein levels of CEA in Ki-ras4BVal-12 transfectant cells were decreased by blocking expression of Ki-ras4BVal-12 with antisense oligonucleotides. N-cadherin levels were decreased in only the Ki-ras transfectants, whereas E-cadherin levels were unchanged. Immunohistochemical analysis demonstrated that Ki-ras4BVal-12 transfectant cells did not polarize into cells with discrete apical and basal regions and so could not restrict expression of CEA to the apical region. These unpolarized cells displayed elevated levels of CEA all along their surface membrane where CEA mediated random, multilayered associations of tumor cells. This aggregation was both calcium-independent and blocked by Fab' fragments of anti-CEA monoclonal antibody col-1. Trafficking of the lysosomal cysteine protease cathepsin B may also be altered when cell polarity cannot be established. Ki-ras4BVal-12 transfectant cells expressed 2-fold elevated protein levels of the lysosomal cysteine protease cathepsin B but did not up-regulate cathepsin B mRNA expression. One function of oncogenic c-Ki-Ras proteins in colon cancer progression may be to up-regulate CEA and thus to prevent the lateral adhesion of adjacent colon epithelial cells that normally form a monolayer in vivo.

Carcinoembryonic Antigen↗