Oct-3/4 is a dose-dependent oncogenic fate determinant

Gidekel, Sharon; Pizov, Galina; Bergman, Yehudit; Pikarsky, Eli

doi:10.1016/s1535-6108(03)00270-8

Cited by 419 publications

(357 citation statements)

References 54 publications

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“…POU5F1 reactivation has been found to be implicated in human tumours; aberrant POU5F1 expression was detected in germ cell tumours [36,37] and recently in bladder cancer [38]. Furthermore, ectopic Pou5f1 expression in adult mice resulted in dysplastic growth of epithelial tissues [39].…”

Section: Discussionmentioning

confidence: 99%

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

Möller

Stenman

Mandahl

et al. 2008

The Journal of Pathology

108

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The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino‐terminal domain and the POU5F1 carboxy‐terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild‐type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

Möller

Stenman

Mandahl

et al. 2008

The Journal of Pathology

108

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“…49 Finally, manipulation in normal stem cells of some self-renewal pathways, such as Oct4, can also lead to cancer. 50 However, it is still unclear whether such tumors arise from 'sick' stem cells or from nonstem (progenitor) cells, which acquire a stem cell-like phenotype during carcinogenesis. Although this hypothesis is for the moment purely based on the altered expression following H. pylori infection of a few transcripts that have previously been identified in stem cells, the involvement of cancer stem cells in tumor initiation would provide an avenue for early detection of samples prone to cancerization.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

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“…All isotypic controls used for immunofluorescence tested negative ( Figure 2B Figure S1, 4,8,12,16,20).…”

Section: Identification and Immunophenotypic Characterization Of Oct-mentioning

confidence: 99%

“…The Octamer-binding transcription factor 4 (Oct-4), together with SOX-2 and NANOG, maintains self-renewal and blocks cell differentiation in embryonic stem cells [12][13][14] and is expressed by some cancer stem cells [15][16][17][18][19][20]. Among these factors, Oct-4 and SOX-2 appear to be indispensable for stemness maintenance [21].…”

Section: Introductionmentioning

confidence: 99%

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

Pezzolo¹,

Parodi²,

Marimpietri³

et al. 2011

Cell Res

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Oct-3/4 is a dose-dependent oncogenic fate determinant

Cited by 419 publications

References 54 publications

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Oct-4+/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells

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