Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research最新文献_第5页

Oncogenic transformation of cells by a conditionally active form of the protein kinase Akt/PKB. 通过条件活化形式的蛋白激酶Akt/PKB对细胞的致癌转化。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-06-01

A M Mirza, A D Kohn, R A Roth, M McMahon

{"title":"Oncogenic transformation of cells by a conditionally active form of the protein kinase Akt/PKB.","authors":"A M Mirza, A D Kohn, R A Roth, M McMahon","doi":"","DOIUrl":"","url":null,"abstract":"The Akt/PKB protein kinase is implicated in the control of cell cycle progression and the suppression of apoptosis in cancer cells. Here we describe the use of a conditionally active form of Akt/PKB (M+ Akt:ER*) to study the ability of this protein to influence biological processes that are central to the process of oncogenic transformation of mammalian cells. Activation of M+ Akt:ER* in Rat1 cells elicited alterations in cell morphology and promoted anchorage-independent growth in agarose with high efficiency. Consistent with these observations, activation of M+ Akt:ER* suppressed the apoptosis of Rat1 cells that occurs after the detachment of these cells from extracellular matrix. Furthermore, activation of M+ Akt:ER* was sufficient to promote the progression of quiescent Rat1 cells into the S and G2-M phases of the cell cycle. In accord with this is the observation that activation of M+ Akt:ER* led to decreased expression of the cyclin-dependent kinase inhibitor p27Kip1 with a concomitant increase in cyclin-dependent kinase-2 activity. Perhaps surprisingly, activation of M+ Akt:ER* or expression of a constitutively active form of Akt led to rapid activation of MAP/ERK Kinase (MEK) and the extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinases in Rat1 cells. However, pharmacological inhibition of MEK by PD098059 did not inhibit the morphological alterations of Rat1 cells that occur after M+ Akt:ER* activation. These data suggest that M+ Akt:ER* can activate a number of pathways in Rat1 cells, leading to significant alterations in a number of biological processes. The conditional transformation system described here will allow further elucidation of the ability of Akt to contribute to both the normal response of cells to mitogenic stimulation and the aberrant proliferation observed in cancer cells.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 6","pages":"279-92"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21750353","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

Cell cycle control during liver development in the rat: evidence indicating a role for cyclin D1 posttranscriptional regulation. 大鼠肝脏发育过程中的细胞周期控制:cyclin D1转录后调控作用的证据

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-06-01

M M Awad, P A Gruppuso

{"title":"Cell cycle control during liver development in the rat: evidence indicating a role for cyclin D1 posttranscriptional regulation.","authors":"M M Awad, P A Gruppuso","doi":"","DOIUrl":"","url":null,"abstract":"Hepatocytes are capable of marked changes in proliferation in response to various physiological and pathophysiological stimuli. Although the changes in adult hepatocyte growth regulation that accompany reduction of liver mass, liver injury, and liver carcinogenesis have come under intense scrutiny, the regulation of hepatocyte growth during the latter stages of development is largely uncharacterized. We have examined hepatic cell cycle control in the developing rat. Analysis of term (fetal day 21) liver and cultured, term hepatocytes revealed G0-G1 growth-arrested cells relative to preterm (fetal day 19) liver and isolated hepatocytes. G1 cyclin-dependent kinase (CDK) activity was correlated with growth arrest at term in both in vivo and in vitro studies. The decline in CDK activity at term could not be attributed to a change in CDK protein content. Rather, the decline in CDK activity was associated with a concomitant decline in cyclin D1 protein content. However, cyclin D1 mRNA levels did not correlate with protein levels. Cyclin D1 mRNA was present at a higher level in adult livers, in which cyclin D1 protein was absent, than in fetal livers. We also examined the phosphorylation (activation) state of p38 mitogen-activated protein kinase, a potential hepatocyte-growth regulator and modulator of cyclin D1 content. p38 activity was inversely related to cyclin D1 content during liver development and regeneration. These data indicate that a posttranscriptional mechanism regulating cyclin D1 content is involved in the temporary hepatocyte growth arrest seen in the perinatal period and in the maintenance of adult hepatocytes in a quiescent state. We speculate that this posttranscriptional regulation may be downstream from the p38 mitogen-activated protein kinase pathway.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 6","pages":"325-34"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21750357","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

The role of p21 in interferon gamma-mediated growth inhibition of human breast cancer cells. p21在干扰素γ介导的人乳腺癌细胞生长抑制中的作用。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-06-01

J L Gooch, R E Herrera, D Yee

{"title":"The role of p21 in interferon gamma-mediated growth inhibition of human breast cancer cells.","authors":"J L Gooch, R E Herrera, D Yee","doi":"","DOIUrl":"","url":null,"abstract":"IFN-gamma-mediated growth inhibition requires signal transducers and activators of transcription (STAT)-1 activation and may require induction of the cyclin-dependent kinase inhibitor p21. Using an electrophoretic mobility shift assay, we identified STAT1 activation after IFN-gamma treatment in breast cancer cell lines. Accordingly, IFN-gamma inhibited proliferation of monolayer cultured MCF-7 and MDA-MB-231 breast cancer cells. Interestingly, IFN-gamma inhibited anchorage-independent growth of MCF-7 cells but had no effect on MDA-MB-231 colony formation. Because p21 has been shown to play a role in anchorage-independent growth and is a transcriptional target of STAT1, we examined the effect of IFN-gamma on p21 mRNA. We found that IFN-gamma induced p21 mRNA in MCF-7 cells but not in MDA-MB-231 cells. Furthermore, IFN-gamma induced activation of a p21 promoter-luciferase reporter construct that contained the STAT1-inducible element in MCF-7 cells, but not in MDA-MB-231 cells. IFN-gamma treatment resulted in increased p21 protein in MCF-7 cells, whereas MDA-MB-231 cells did not appear to express detectable p21, even after IFN-gamma treatment. However, in MDA-MB-231 cells, p21 protein was detected only after proteosome inhibition, suggesting that degradation may be responsible for the undetectable level of p21 in these cells, despite the abundant mRNA levels. Finally, focus formation of MDA-MB-231 cells was inhibited by overexpression of p21. In conclusion, STAT1 activation does not appear to be sufficient for IFN-gamma-mediated growth inhibition. Furthermore, the role of p21 appears to be complex because monolayer growth inhibition occurs in the absence of p21, but anchorage-independent growth inhibition may require p21. Breast cancer cells may provide a unique model for further study of IFN-gamma signaling.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 6","pages":"335-42"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21750358","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-mediated differentiation of the erythroleukemia cell line K562. p53介导的红细胞K562的分化。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-06-01

K Chylicki, M Ehinger, H Svedberg, G Bergh, I Olsson, U Gullberg

{"title":"p53-mediated differentiation of the erythroleukemia cell line K562.","authors":"K Chylicki, M Ehinger, H Svedberg, G Bergh, I Olsson, U Gullberg","doi":"","DOIUrl":"","url":null,"abstract":"The tumor suppressor gene p53 can mediate both apoptosis and cell cycle arrest. In addition, p53 also influences differentiation. To further characterize the differentiation inducing properties of p53, we overexpressed a temperature-inducible p53 mutant (ptsp53Val135) in the erythroleukemia cell line K562. The results show that wild-type p53 and hemin synergistically induce erythroid differentiation of K562 cells, indicating that p53 plays a role in the molecular regulation of differentiation. However, wild-type p53 did not affect phorbol 12-myristate 13-acetate-dependent appearance of the megakaryocyte-related cell surface antigens CD9 and CD61, suggesting that p53 does not generally affect phenotypic modulation. The cyclin-dependent kinase inhibitor p21, a transcriptional target of p53, halts the cell cycle in G1 and has also been implicated in the regulation of differentiation and apoptosis. However, transiently overexpressed p21 did neither induce differentiation nor affect the cell cycle distribution or viability of K562 cells, suggesting that targets downstream of p53 other than p21 are critical for the p53-mediated differentiation response.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 6","pages":"315-24"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21750356","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

Specific inhibition of growth factor-stimulated extracellular signal-regulated kinase 1 and 2 activation in intact cells by electroporation of a growth factor receptor-binding protein 2-Src homology 2 binding peptide. 电穿孔生长因子受体结合蛋白2- src同源2结合肽对完整细胞中生长因子刺激的细胞外信号调节激酶1和2活化的特异性抑制

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-06-01

L Raptis, H L Brownell, A M Vultur, G M Ross, E Tremblay, B E Elliott

{"title":"Specific inhibition of growth factor-stimulated extracellular signal-regulated kinase 1 and 2 activation in intact cells by electroporation of a growth factor receptor-binding protein 2-Src homology 2 binding peptide.","authors":"L Raptis, H L Brownell, A M Vultur, G M Ross, E Tremblay, B E Elliott","doi":"","DOIUrl":"","url":null,"abstract":"Activation of the Ras pathway is central to mitogenesis by a variety of growth factors such as the epidermal growth factor, platelet-derived growth factor, or hepatocyte growth factor. Ras activation requires the function of adaptors such as growth factor receptor-binding protein 2, which can bind either directly or indirectly through Src homology 2 domains to the activated receptor. To examine the role of the Src homology 2 domain of growth factor receptor-binding protein 2 in the mitogenic response triggered by these growth factors, we introduced a peptide (PVPE-phosphono-methylphenylalanine-INQS) that can selectively bind this domain into mouse, rat, or human cells growing on conductive indium-tin oxide-coated glass by in situ electroporation. Cells were subsequently stimulated with growth factors and assessed for activation of a downstream target, extracellular signal-regulated kinase (ERK) 1/2, by probing with antibodies specific for its activated form. Electrodes and slides were configured to provide nonelectroporated control cells side by side with the electroporated ones, both growing on the same type of indium-tin oxide-coated glass surface. The data demonstrate that the peptide can cause a dramatic inhibition of epidermal growth factor or platelet-derived growth factor-mediated ERK1/2 activation and DNA synthesis in vivo, compared with its control phenylalanine-containing counterpart. In contrast, the peptide had a very limited effect on hepatocyte growth factor-triggered ERK1/2 activation and DNA synthesis. These results demonstrate the potential of the in situ electroporation approach described here in the study of the coupling of activated receptor tyrosine kinases to the ERK1/2 cascade.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 6","pages":"293-303"},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21750354","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

Genistein regulation of transforming growth factor-alpha, epidermal growth factor (EGF), and EGF receptor expression in the rat uterus and vagina. 染料木素对大鼠子宫和阴道中转化生长因子- α、表皮生长因子(EGF)及EGF受体表达的调控。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-05-01

N M Brown, C A Lamartiniere

{"title":"Genistein regulation of transforming growth factor-alpha, epidermal growth factor (EGF), and EGF receptor expression in the rat uterus and vagina.","authors":"N M Brown, C A Lamartiniere","doi":"","DOIUrl":"","url":null,"abstract":"Epidemiological reports and laboratory data have associated soy and genistein with reduced incidence of uterine, breast, and prostate cancers, cardiovascular disease and osteoporosis, and lower total blood cholesterol. The aim of this study was to investigate the effect of genistein in the uterus and vagina of rats, focusing our attention on the distribution of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and EGF receptor. A pharmacological dose of genistein (500 microg/g body weight) injected in rats on days 16,18, and 20 postpartum resulted in significant uterine wet weight gain, with hypertrophy of the luminal and glandular epithelium of the uteri, and squamous epithelium of the vagina in 21-day-old animals. At 50 days of age, hypertrophy was no longer evident in the uterus and vagina. Prepubertal genistein treatment resulted in significantly increased EGF immunostaining in individual stromal cells and reduced EGF receptor immunostaining in blood vessels of the uterus. Genistein-treated rats had decreased TGF-alpha immunostaining in glandular and luminal epithelium and a slight increase in EGF receptor immunostaining in stromal cells of the uterus. This suggests paracrine interaction between cells elevating the level of EGF ligand in the stroma and the EGF receptor in the luminal and glandular epithelium, resulting in uterine hypertrophy. In the vagina, genistein did not cause significant alterations to the EGF-signaling pathway in 21- and 50-day-old rats. We conclude that pharmacological doses of genistein during the prepubertal period can modulate the EGF-signaling pathway in the uterus and exert a uterotrophic response in a short-term manner.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 5","pages":"255-60"},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21688939","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

Accelerated development of polyoma tumors and embryonic lethality: different effects of p53 loss on related mouse backgrounds. 多瘤肿瘤的加速发展和胚胎致死:p53缺失对相关小鼠背景的不同影响。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-05-01

D C Dey, R P Bronson, J Dahl, J P Carroll, T L Benjamin

引用次数: 0

The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism. 新型三萜2-氰-3,12-二氧库林-1,9-二烯-28-oic酸通过caspase-8依赖机制诱导人髓系白血病细胞凋亡。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-05-01

Y Ito, P Pandey, A Place, M B Sporn, G W Gribble, T Honda, S Kharbanda, D Kufe

{"title":"The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism.","authors":"Y Ito, P Pandey, A Place, M B Sporn, G W Gribble, T Honda, S Kharbanda, D Kufe","doi":"","DOIUrl":"","url":null,"abstract":"The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a multifunctional molecule that induces growth inhibition and differentiation of human myeloid leukemia cells. The present studies demonstrate that CDDO treatment results in apoptosis of U-937 and HL-60 myeloid leukemia cells. Similar to 1-beta-D-arabinofuranosylcytosine (ara-C), another agent that inhibits growth and induces apoptosis of these cells, CDDO induced the release of mitochondrial cytochrome c and activation of caspase-3. Overexpression of Bcl-X(L) blocked cytochrome c release, caspase-3 activation, and apoptosis in ara-C-treated cells. By contrast, CDDO-induced release of cytochrome c, and activation of caspase-3 were diminished only in part by Bcl-X(L). In concert with these findings, we demonstrate that CDDO, but not ara-C, activates caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism. The results also show that CDDO-induced cytochrome c release is mediated by caspase-8-dependent cleavage of Bid. These findings demonstrate that CDDO induces apoptosis of myeloid leukemia cells and that this novel agent activates an apoptotic signaling cascade distinct from that induced by the cytotoxic agent ara-C.","PeriodicalId":9753,"journal":{"name":"Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research","volume":"11 5","pages":"261-7"},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21690071","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

Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors. 暴露于蛋白酶体抑制剂后p53在细胞周期调节和细胞凋亡中的作用。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-05-01

F Chen, D Chang, M Goh, S A Klibanov, M Ljungman

引用次数: 0

Calpain inhibitor 1 activates p53-dependent apoptosis in tumor cell lines. Calpain inhibitor 1激活肿瘤细胞系p53依赖性细胞凋亡。

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Pub Date : 2000-05-01

I A Atencio, M Ramachandra, P Shabram, G W Demers

引用次数: 0