A comparison of the effects of prosthetic and commercially pure metals on retrieved human fibroblasts: The role of surface elemental composition

AbstractCancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.

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On the useful role of OH free radicals in differentiation of cultured human fibroblasts

Archives of Gerontology and Geriatrics ◽

10.1016/s0167-4943(00)00084-4 ◽

2000 ◽

Vol 31 (3) ◽

pp. 233-242 ◽

Cited By ~ 9

Author(s):

Enikö Bazsó-Dombi ◽

Katalin Oravecz ◽

Florence Jeney ◽

Katalin Nagy ◽

Imre Zs.-Nagy

Keyword(s):

Free Radicals ◽

Human Fibroblasts ◽

Cultured Human Fibroblasts

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Wettability and osteoblastic cell adhesion on ultrapolished commercially pure titanium surfaces: the role of the oxidation and pollution states

Journal of Adhesion Science and Technology ◽

10.1080/01694243.2014.893815 ◽

2014 ◽

Vol 28 (12) ◽

pp. 1207-1218 ◽

Cited By ~ 5

Author(s):

Miguel A. Fernández-Rodríguez ◽

Alda Y. Sánchez-Treviño ◽

Elvira De Luna-Bertos ◽

Javier Ramos-Torrecillas ◽

Olga García-Martínez ◽

...

Keyword(s):

Cell Adhesion ◽

Pure Titanium ◽

Osteoblastic Cell ◽

Commercially Pure Titanium ◽

Commercially Pure ◽

Titanium Surfaces

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Evidence for a role of calmodulin in serum stimulation of Na+ influx in human fibroblasts.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.79.11.3537 ◽

1982 ◽

Vol 79 (11) ◽

pp. 3537-3541 ◽

Cited By ~ 69

Author(s):

N. E. Owen ◽

M. L. Villereal

Keyword(s):

Human Fibroblasts ◽

Serum Stimulation ◽

Stimulation Of

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Peroxisomal membrane proteins are properly targeted to peroxisomes in the absence of COPI- and COPII-mediated vesicular transport

Journal of Cell Science ◽

10.1242/jcs.114.11.2199 ◽

2001 ◽

Vol 114 (11) ◽

pp. 2199-2204 ◽

Cited By ~ 1

Author(s):

Tineke Voorn-Brouwer ◽

Astrid Kragt ◽

Henk F. Tabak ◽

Ben Distel

Keyword(s):

Endoplasmic Reticulum ◽

Membrane Proteins ◽

Secretory Pathway ◽

Human Fibroblasts ◽

Vesicle Transport ◽

Peroxisome Biogenesis ◽

Peroxisomal Membrane ◽

Classic Model ◽

Early Secretory Pathway

The classic model for peroxisome biogenesis states that new peroxisomes arise by the fission of pre-existing ones and that peroxisomal matrix and membrane proteins are recruited directly from the cytosol. Recent studies challenge this model and suggest that some peroxisomal membrane proteins might traffic via the endoplasmic reticulum to peroxisomes. We have studied the trafficking in human fibroblasts of three peroxisomal membrane proteins, Pex2p, Pex3p and Pex16p, all of which have been suggested to transit the endoplasmic reticulum before arriving in peroxisomes. Here, we show that targeting of these peroxisomal membrane proteins is not affected by inhibitors of COPI and COPII that block vesicle transport in the early secretory pathway. Moreover, we have obtained no evidence for the presence of these peroxisomal membrane proteins in compartments other than peroxisomes and demonstrate that COPI and COPII inhibitors do not affect peroxisome morphology or integrity. Together, these data fail to provide any evidence for a role of the endoplasmic reticulum in peroxisome biogenesis.

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Accumulation of soluble and nucleolar-associated p53 proteins following cellular stress

Journal of Cell Science ◽

10.1242/jcs.114.10.1867 ◽

2001 ◽

Vol 114 (10) ◽

pp. 1867-1873 ◽

Cited By ~ 1

Author(s):

S.A. Klibanov ◽

H.M. O'Hagan ◽

M. Ljungman

Keyword(s):

Target Genes ◽

Uv Light ◽

Human Fibroblasts ◽

Proteasome Inhibition ◽

Tumor Suppressor P53 ◽

Mdm2 Protein ◽

Transcription Inhibitor ◽

Cellular Stresses ◽

In Cells

The tumor suppressor p53 is a nucleocytoplasmic shuttling protein that accumulates in the nucleus of cells exposed to various cellular stresses. One important role of nuclear p53 is to mobilize a stress response by transactivating target genes such as the p21(Waf1) gene. In this study, we investigated more closely the localization of p53 in cells following various stresses. Immunocytochemistry of fixed human fibroblasts treated with either UV light, the kinase and transcription inhibitor DRB or the proteasome inhibitor MG132 revealed abundant p53 localized to the nucleus. When cells treated with UV or DRB were permeabilized prior to fixation to allow soluble proteins to diffuse, the nuclear p53 signal was abolished. However, in cells treated with MG132, residual p53 localized to distinct large foci. Furthermore, nucleolin co-localized with p53 to these foci, suggesting that these foci were nucleolar structures. Interestingly, the MDM2 protein was found to co-localize with p53 to nucleolar structures following proteasome inhibition. Our results suggest that the p53 proteins accumulating in the nucleus following UV-irradiation or blockage of transcription are freely soluble and, thus, should be able to roam the nucleus to ensure high occupancy of p53 binding sites. However, inhibition of proteasome activity may be a unique stress in that it leads to the sequestering of p53 proteins to the nucleolus, thereby blunting the p53-mediated transactivation of target genes.

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Role of p14ARF in Replicative and Induced Senescence of Human Fibroblasts

Molecular and Cellular Biology ◽

10.1128/mcb.21.20.6748-6757.2001 ◽

2001 ◽

Vol 21 (20) ◽

pp. 6748-6757 ◽

Cited By ~ 143

Author(s):

Wenyi Wei ◽

Ruth M. Hemmer ◽

John M. Sedivy

Keyword(s):

Replicative Senescence ◽

Human Fibroblasts ◽

Growth Arrest ◽

Fibroblast Cell ◽

Cell Types ◽

Major Pathway ◽

Telomere Shortening ◽

Normal Human ◽

Cell Strains

ABSTRACT Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53−/− and p21−/− human fibroblast cell strains constructed by gene targeting to investigate the involvement of the Arf-Mdm2-p53-p21 pathway in natural as well as premature senescence states. We propose that in cell types that upregulate p21 during replicative exhaustion, such as normal human fibroblasts, p53, p21, and Rb act sequentially and constitute the major pathway for establishing growth arrest and that the telomere-initiated signal enters this pathway at the level of p53. Our results also revealed a number of significant differences between human and rodent fibroblasts in the regulation of senescence pathways.

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