Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line.
Journal
Stem cells international
ISSN: 1687-966X
Titre abrégé: Stem Cells Int
Pays: United States
ID NLM: 101535822
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
01
2019
revised:
17
05
2019
accepted:
04
07
2019
entrez:
31
12
2019
pubmed:
31
12
2019
medline:
31
12
2019
Statut:
epublish
Résumé
Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene expression profiles of these transcription factors in cervical cancer samples and found that they are preferentially expressed in the tumor component. Also, cancer stem cell-enriched cultures grown as sphere cultures showed overexpression of OSKM-N genes. Importantly, we observed that lentiviral-mediated transduction of these factors confers, to a nontumorigenic immortalized human cell line, properties of cancer stem cells as the ability to form tumors in a mouse model. When we performed a meta-analysis using microarray data from cervical cancer biopsies and normal tissues, we found that the expression of OSKM-N and some target genes allowed separating tumor and normal tissues between samples, which enhanced the importance of OSKM-N in the tumorigenesis. Finally, we analyzed and compared both transcript and protein expression profiles of these factors within a cohort of patients with cervical cancer. To our knowledge, this is the first time that the expression of OSKM-N is described to induce one of the main characteristics of the cancer stem cell, the tumorigenicity. And, more importantly, its exogenous expression in a nontumorigenic cell line is sufficient to induce a tumorigenic phenotype; furthermore, the differential expression of this transcription factor distinguishes tumor tissue and normal tissue in cervical samples.
Identifiants
pubmed: 31885625
doi: 10.1155/2019/7683817
pmc: PMC6914900
doi:
Types de publication
Journal Article
Langues
eng
Pagination
7683817Informations de copyright
Copyright © 2019 Graciela Ruiz et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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