Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research最新文献_第9页

A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase. TrkB/胰岛素受体相关受体嵌合受体诱导PC12细胞分化并表现出丝裂原活化蛋白激酶的延长活化。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-12-01

K S Kelly-Spratt, L J Klesse, J Merenmies, L F Parada

{"title":"A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase.","authors":"K S Kelly-Spratt, L J Klesse, J Merenmies, L F Parada","doi":"","DOIUrl":"","url":null,"abstract":"Insulin receptor-related receptor (IRR), an orphan receptor in the insulin receptor (IR) family of receptor tyrosine kinases, is primarily localized to neural crest-derived sensory neurons during embryonic development. Expression of IRR closely resembles that of the nerve growth factor receptor, TrkA. To analyze the signaling properties and function of IRR in PC12 cells, a TrkB/IRR hybrid receptor was used. In contrast to IR activation, brain-derived neurotrophic growth factor-mediated activation of the TrkB/IRR receptor resulted in differentiation rather than proliferation. Analysis of cytoplasmic substrates activated by the TrkB/IRR receptor indicates a signaling pathway similar to that of the IR. Mutagenesis studies further show that only TrkB/IRR receptors able to phosphorylate mitogen-activated protein kinase elicit a differentiation response. Our analysis indicates that prolonged kinetics of mitogen-activated protein kinase activation mediated by the TrkB/IRR chimeric receptor correlates with induction to differentiate.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 12","pages":"805-12"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21473723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A genetic analysis of PAX3-FKHR, the oncogene of alveolar rhabdomyosarcoma. 肺泡横纹肌肉瘤癌基因PAX3-FKHR的基因分析。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-12-01

B E Kempf, P K Vogt

引用次数: 0

Stabilization and reactivation of the p53 tumor suppressor protein in nontumorigenic revertants of HeLa cervical cancer cells. 非致瘤性HeLa宫颈癌细胞中p53肿瘤抑制蛋白的稳定和再激活。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

M Athanassiou, Y Hu, L Jing, B Houle, H Zarbl, A M Mikheev

{"title":"Stabilization and reactivation of the p53 tumor suppressor protein in nontumorigenic revertants of HeLa cervical cancer cells.","authors":"M Athanassiou, Y Hu, L Jing, B Houle, H Zarbl, A M Mikheev","doi":"","DOIUrl":"","url":null,"abstract":"We demonstrated previously that loss of in vitro transformation and in vivo tumorigenicity in two independent revertant clones of HeLa cells (designated HA and HF) resulted from dominant-acting genetic changes. Analysis of the p53 tumor suppressor gene revealed stabilization and at least partial restoration of wild-type p53 transactivation properties pathways in both revertants of HPV-induced cell transformation. The half-lives of the p53 protein and both of the HA and HF clones were increased approximately 4 fold compared with the parental HeLa cells (16, 17, and 4 min, respectively). The levels of E6 viral protein expression were similar in the three cell lines, whereas the levels of the ubiquitin ligase protein, E6 associated protein (E6-AP), were elevated in the revertants. Western blot analysis of immunoaffinity-purified p53 demonstrated that stabilization of p53 in the revertants was correlated with a reduction in the in vivo formation of complexes involving the E6 oncoprotein and p53. Stabilization of p53 function in the revertants did not result from mutations in either the p53 or E6-AP genes. Despite the observed stabilization and restoration of p53 transactivation function in the revertants, exposure of the revertants to DNA-damaging agents did not result in elevated levels of p21(waf-1) protein and failed to induce growth arrest in the G1 phase of the cell cycle. However, p53-independent induction of p21(waf-1) protein also failed to induce the G1 phase of the cell cycle. Thus, restoration of wild-type p53 transactivation activity in the HA and HF revertants is insufficient to induce G1 arrest and reversion from HPV-induced cell transformation in our model system.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"729-37"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Relationship between DNA adduct levels, repair enzyme, and apoptosis as a function of DNA methylation by azoxymethane. DNA加合物水平、修复酶和细胞凋亡在偶氮甲烷甲基化作用下的关系。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

M Y Hong, R S Chapkin, C P Wild, J S Morris, N Wang, R J Carroll, N D Turner, J R Lupton

{"title":"Relationship between DNA adduct levels, repair enzyme, and apoptosis as a function of DNA methylation by azoxymethane.","authors":"M Y Hong, R S Chapkin, C P Wild, J S Morris, N Wang, R J Carroll, N D Turner, J R Lupton","doi":"","DOIUrl":"","url":null,"abstract":"DNA alkylating agent exposure results in the formation of a number of DNA adducts, with O6-methyl-deoxyguanosine (O6-medG) being the major mutagenic and cytotoxic DNA lesion. Critical to the prevention of colon cancer is the removal of O6-medG DNA adducts, either through repair, for example, by O6-alkylguanine-DNA alkyltransferase (ATase) or targeted apoptosis. We report how rat colonocytes respond to administration of azoxymethane (a well-characterized experimental colon carcinogen and DNA-methylating agent) in terms of O6-medG DNA adduct formation and adduct removal by ATase and apoptosis. Our results are: (a) DNA damage is greater in actively proliferating cells than in the differentiated cell compartment; (b) expression of the DNA repair enzyme ATase was not targeted to the proliferating cells or stem cells but rather is confined primarily to the upper portion of the crypt; (c) apoptosis is primarily targeted to the stem cell and proliferative compartments; and (d) the increase in DNA repair enzyme expression over time in the bottom one-third of the crypt corresponds with the decrease in apoptosis in this same crypt region.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"749-58"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin. 鸟氨酸脱羧酶水平升高对皮肤细胞周期进程的影响。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

S K Gilmour, M Birchler, M K Smith, K Rayca, J Mostochuk

{"title":"Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin.","authors":"S K Gilmour, M Birchler, M K Smith, K Rayca, J Mostochuk","doi":"","DOIUrl":"","url":null,"abstract":"By crossing TG.AC v-Ha-ras and K6/ODC transgenic mice, we found previously that an activated ras and follicular ornithine decarboxylase (ODC) overexpression cooperate to generate spontaneous tumors in the skin. Cellular proliferation was dramatically increased in the K6/ODC transgenic skin, as evidenced by elevated proliferating cell nuclear antigen and Ki67 expression compared with nontransgenic littermates. Keratinocytes isolated from transgenic skin also displayed increased clonal growth. Paradoxically, expression of the growth inhibition-associated proteins p53, p21Waf1, p27Klp1, and Bax was increased with ODC overexpression in the skin. ODC overexpression did not affect cyclin D/cyclin-dependent kinase 4 (Cdk4)-dependent phosphorylation of retinoblastoma protein but stimulated cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity, with minimal effect on the levels of these proteins. Thus, ODC/polyamine-induced activation of cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity may cooperate with the ras induction of cyclin D/Cdk4/6-associated retinoblastoma protein phosphorylation to not only stimulate proliferation but ultimately contribute to tumor development.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"739-48"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteolysis of heat shock transcription factor is associated with apoptosis in rat Nb2 lymphoma cells. 热休克转录因子蛋白水解与大鼠Nb2淋巴瘤细胞凋亡有关。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

M Zhang, M J Blake, P W Gout, D J Buckley, A R Buckley

{"title":"Proteolysis of heat shock transcription factor is associated with apoptosis in rat Nb2 lymphoma cells.","authors":"M Zhang, M J Blake, P W Gout, D J Buckley, A R Buckley","doi":"","DOIUrl":"","url":null,"abstract":"Previously, we reported that prolactin (PRL)-dependent Nb2 lymphoma cells exhibit an aberrant heat shock response because of cysteine protease-mediated fragmentation of the heat shock transcription factor (HSF). Moreover, exposure of the cells to PRL abrogated heat-induced HSF proteolysis. The present study was conducted to investigate whether HSF proteolysis is a component of the apoptotic process in this model. Initially, the effect of heat stress (41 degrees C for 1 h) on apoptosis, determined by agarose gel electrophoresis and flow cytometric analysis, was evaluated in PRL-dependent Nb2-11 cells and in an autonomous subline (Nb2-SFJCD1). Heat was found to induce HSF proteolysis concomitant with activation of apoptosis in each cell line; treatment with PRL blocked these effects. To determine whether HSF proteolysis occurred as a generalized phenomenon associated with apoptosis, the effects of other activators of this process were evaluated. Vinblastine, cycloheximide, and thapsigargin stimulated fragmentation of HSF and hydrolysis of DNA in each cell line. The addition of PRL blocked the effects of vinblastine but was ineffective in cells treated with either cycloheximide or thapsigargin. Iodoacetamide, a cysteine protease inhibitor that blocks HSF fragmentation, also inhibited apoptosis. In addition, Z-VAD, a general caspase antagonist, blocked vinblastine-induced fragmentation of HSF and DNA, suggesting that the enzyme responsible for proteolysis of the transcription factor was likely a caspase family member. The results suggest that proteolysis of HSF reflects the action of one or more caspases activated as a consequence of stimulation of cell death. It is concluded that HSF may represent a previously unrecognized substrate for caspases or other cysteine proteases activated during apoptosis.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"759-67"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BUBR1 phosphorylation is regulated during mitotic checkpoint activation. BUBR1磷酸化在有丝分裂检查点激活过程中受到调节。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

W Li, Z Lan, H Wu, S Wu, J Meadows, J Chen, V Zhu, W Dai

{"title":"BUBR1 phosphorylation is regulated during mitotic checkpoint activation.","authors":"W Li, Z Lan, H Wu, S Wu, J Meadows, J Chen, V Zhu, W Dai","doi":"","DOIUrl":"","url":null,"abstract":"Eukaryotic cells have evolved a mechanism that delays the progression of mitosis until condensed chromosomes are properly positioned on the mitotic spindle. To understand the molecular basis of such monitoring mechanism in human cells, we have been studying genes that regulate the mitotic checkpoint. Our early studies have led to the cloning of a full-length cDNA encoding MAD3-like protein (also termed BUBR1/MAD3/SSK1). Dot blot analyses show that BUBR1 mRNA is expressed in tissues with a high mitotic index but not in differentiated tissues. Western blot analyses show that in asynchronous cells, BUBR1 protein primarily exhibits a molecular mass of 120 kDa, and its expression is detected in most cell lines examined. In addition, BUBR1 is present during various stages of the cell cycle. As cells enter later S and G2, BUBR1 levels are increased significantly. Nocodazole-arrested mitotic cells obtained by mechanical shake-off contain BUBR1 antigen with a slower mobility on denaturing SDS gels. Phosphatase treatment restores the slowly migrating band to the interphase state, indicating that the slow mobility of the BUBR1 antigen is attributable to phosphorylation. Furthermore, purified recombinant His6-BUBR1 is capable of autophosphorylation. Our studies indicate that BUBR1 phosphorylation status is regulated during spindle disruption. Considering its strong homology to BUB1 protein kinase, BUBR1 may also play an important role in mitotic checkpoint control by phosphorylation of a critical cellular component(s) of the mitotic checkpoint pathway.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"769-75"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of insulin-like growth factor I receptor-dependent expression of p107 and cyclin A in cells that lack the extracellular matrix protein secreted protein acidic and rich in cysteine. 在缺乏细胞外基质蛋白的细胞中，缺乏胰岛素样生长因子I受体依赖性的p107和细胞周期蛋白A的表达，分泌酸性和富含半胱氨酸的蛋白。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-11-01

A Basu, U Rodeck, G C Prendergast, C C Howe

{"title":"Loss of insulin-like growth factor I receptor-dependent expression of p107 and cyclin A in cells that lack the extracellular matrix protein secreted protein acidic and rich in cysteine.","authors":"A Basu, U Rodeck, G C Prendergast, C C Howe","doi":"","DOIUrl":"","url":null,"abstract":"The extracellular matrix-associated glycoprotein secreted protein acidic and rich in cysteine (SPARC) has been implicated in the control of cell proliferation during tissue remodeling, wound healing, and malignant development. Here, we describe a novel mechanism through which SPARC influences cell cycle progression in embryonic fibroblasts derived from Sparc-nullizygous (-/-) mice. SPARC-deficient cells were indistinguishable from wild-type cells in their ability to initiate DNA synthesis after treatment with either fetal bovine serum or platelet-derived growth factor. In contrast, Sparc -/- cells responded poorly to activation of the insulin-like growth factor receptor (IGFI-R) by insulin. This defect was traced to reduced expression of the IGFI-R in Sparc -/- cells. Consistent with impaired cell cycle progression through S-phase, insulin-stimulated Sparc -/- cells also revealed reduced expression of two key regulators of S phase progression (cyclin A and thymidine kinase), whereas expression of the G1 phase progression regulators cmyc or cyclin D1 was unaffected. An examination of the status of retinoblastoma family pocket proteins in Sparc -/- cells revealed a selective and dramatic reduction in levels of the retinoblastoma-related protein p107. Exogenous platelet-derived growth factor restored expression of the IGFI-R and IGFI-R dependent DNA synthesis as well as induction of cyclin A, thymidine kinase, and p107 in insulin-stimulated Sparc -/- cells. These results suggest that SPARC-dependent matrix to cell interactions contribute to the regulation of p107 and cyclin A through IGFI-R dependent pathway(s).","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 11","pages":"721-8"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21452486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

p53 controls low DNA damage-dependent premeiotic checkpoint and facilitates DNA repair during spermatogenesis. p53控制低DNA损伤依赖性减数分裂前检查点，促进精子发生过程中的DNA修复。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-10-01

D Schwartz, N Goldfinger, Z Kam, V Rotter

引用次数: 0

Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin. 丁酸盐诱导结肠癌细胞凋亡级联:β -catenin- tcf通路的调节，与舒林酸和曲古抑素A的作用一致，但与姜黄素无关。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 1999-10-01

M Bordonaro, J M Mariadason, F Aslam, B G Heerdt, L H Augenlicht

{"title":"Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin.","authors":"M Bordonaro, J M Mariadason, F Aslam, B G Heerdt, L H Augenlicht","doi":"","DOIUrl":"","url":null,"abstract":"Short-chain fatty acids play a critical role in colonic homeostasis because they stimulate pathways of growth arrest, differentiation, and apoptosis. These effects have been well characterized in colonic cell lines in vitro. We investigated the role of beta-catenin-Tcf signaling in these responses to butyrate and other well-characterized inducers of apoptosis of colonic epithelial cells. Unlike wild-type APC, which down-regulates Tcf activity, butyrate, as well as sulindac and trichostatin A, all inducers of G0-G1 cell cycle arrest and apoptosis in the SW620 colonic carcinoma cell line, up-regulate Tcf activity. In contrast, structural analogues of butyrate that do not induce cell cycle arrest or apoptosis and curcumin, which stimulates G2-M arrest without inducing apoptosis, do not alter Tcf activity. Similar to the cell cycle arrest and apoptotic cascade induced by butyrate, the up-regulation of Tcf activity is dependent upon the presence of a mitochondrial membrane potential, unlike the APC-induced down-regulation, which is insensitive to collapse of the mitochondrial membrane potential. Moreover, the butyrate-induced increase in Tcf activity, which is reflected in an increase in beta-catenin-Tcf complex formation, is independent of the down-regulation caused by expression of wild-type APC. Thus, butyrate and wild-type APC have different and independent effects on beta-catenin-Tcf signaling. These data are consistent with other reports that suggest that the absence of wild-type APC, associated with the up-regulation of this signaling pathway, is linked to the probability of a colonic epithelial cell entering an apoptotic cascade.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"10 10","pages":"713-20"},"PeriodicalIF":0.0,"publicationDate":"1999-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21407798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0