Expression of Oct4, a Stem Cell Marker, in the Hamster Pancreatic Cancer Model

doi:10.1159/000094317

Pancreatology

Volume 6, Issue 4, August 2006, Pages 406-413

https://doi.org/10.1159/000094317 Get rights and content

Abstract

Background: Oct4 has been shown to present a stem cell marker that is expressed in embryonic cells and in germ cell tumors. Recently, its expression in a few human tissues and cancer cells has been reported. Because in the hamster pancreatic cancer model most tumors develop from within islets presumably from stem cells, we investigated the expression of Oct4 in this model.Methods: Two normal pancreases and 15 pancreatic cancers induced by /V-nitrosobis(2-oxypropyl)amine (BOP) were processed for immunohistochemistry using a monoclonal Oct4 antibody at a concentration of 1:500.Results: In the normal pancreas, Oct4 was expressed only in islet cells in a diffuse cytoplasmic pattern. No nuclear staining was found in any cells. In 14 of the pancreatic cancers, nuclear staining was detected in many cells or in small foci. Diffuse cytoplasmic but no nuclear staining was found in one tumor and a mixed Golgi type and nuclear staining in two cases. Nuclear staining was also identified in early intrainsular ductular and in Ca in situ lesions. Conclusions: BOP reactivates the Oct4 gene and can be considered an early tumor marker in this model.

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Aberrant transcription factors in the cancers of the pancreas
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Citation Excerpt :
Suppression of OCT4 via its negative regulator miR-335 showed similar inhibition of cancer progression in both cell lines, 3D cultures and cancer tissue models [182]. OCT4 nuclear expression was detected in N-nitrosobis(2-oxypropyl)amine (BOP) induced hamster PDAC model [183]. These findings suggest that OCT4 can serve as a therapeutic target for PDAC treatment.
Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-β/SMAD, WNT/β-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.
Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of β-catenin
2016, Phytomedicine
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β-catenin regulates cell-to-cell adhesion and plays a crucial role in Wnt signaling, acting as a transcription cofactor with T cell/lymphoid enhancer factor (TCF) (Ponti et al., 2005). Wnt signaling activation results in the cytoplasmic accumulation of β-catenin and its consequent translocation into the nucleus (Iki and Pour, 2006). Aberrant β-catenin expression is frequently observed in various cancers, including colorectal cancers, lung cancers, breast cancers and head and neck squamous cell carcinoma (Lee et al., 2014).
Aberrant expression of β-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of β-catenin.
In vitro effects of EGCG on the transcription, translation, or degradation of β-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and β-catenin expression was checked in HNC patients’ samples.
β-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of β-catenin signaling. Knockdown of β-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of β-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of β-catenin. The suppression of β-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits β-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation.
This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs.
Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer
2016, Cancer Letters
Citation Excerpt :
Additionally, Nanog and Oct4 have been identified as two of four factors essential for the reprogramming of somatic cells into induced pluripotent stem (iPS) cells [24]. Some studies have suggested that the expression of Nanog and Oct4 is increased during the dedifferentiation process of cancer cells and the oncogenic transformation of somatic cells [25,26]. Thus, Nanog and Oct4 play functional roles and are overexpressed in CSCs, and their upregulation in tumor tissues is correlated with the poor prognosis of patients with lung and oral cancers [27,28].
Helicobacter pylori (H. pylori) infection is considered a major risk factor for gastric cancer. CagA behaves as a major bacterial oncoprotein playing a key role in H. pylori-induced tumorigenesis. Cancer stem cells (CSCs) are believed to possess the ability to initiate tumorigenesis and promote progression. Although studies have suggested that cancer cells can exhibit CSC-like properties in the tumor microenvironment, it remains unclear whether H. pylori infection could induce the emergence of CSC-like properties in gastric cancer cells and, the underlying mechanism. Here, gastric cancer cells were co-cultured with a CagA-positive H. pylori strain or a CagA isogenic mutant strain. We found that H. pylori-infected gastric cancer cells exhibited CSC-like properties, including an increased expression of CSC specific surface markers CD44 and Lgr5, as well as that of Nanog, Oct4 and c-myc, which are known pluripotency genes, and an increased capacity for self-renewal, whereas these properties were not observed in the CagA isogenic mutant strain-infected cells. Further studies revealed that H. pylori activated Wnt/β-catenin signaling pathway in a CagA-dependent manner and that the activation of this pathway was dependent upon CagA-positive H. pylori-mediated phosphorylation of β-catenin at the C-terminal Ser675 and Ser552 residues in a c-met- and/or Akt-dependent manner. We further demonstrated that this activation was responsible for H. pylori-induced CSC-like properties. Moreover, we found the promoter activity of Nanog and Oct4 were upregulated, and β-catenin was observed to bind to these promoters during H. pylori infection, while a Wnt/β-catenin inhibitor suppressed promoter activity and binding. Taken together, these results suggest that H. pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote CSC-like properties in gastric cancer cells.
Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis
2012, World Journal of Gastroenterology
Initiation of Cancer: The Journey From Mutations in Somatic Cells to Epigenetic Changes in Tissue-resident VSELs
2024, Stem Cell Reviews and Reports
OCT4-positive circulating tumor cells may predict a poor prognosis in patients with metastatic castration-resistant prostate cancer treated with abiraterone plus prednisone therapy
2023, Oncology Letters

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Expression of Oct4, a Stem Cell Marker, in the Hamster Pancreatic Cancer Model

Abstract

Mech Dev

Cell

Cancer Cell

Cancer Cell

Differentiation

Oct-4: gatekeeper in the beginnings of mammalian development

Stem Cells

In line with our ancestors: Oct-4 and the mammalian germ

Bioessays

Quantitative expression of Oct-3/4 defi nes differentiation, dedifferentiation or self-renewal of ES cells

Nat Genet

In situ hybridization localizes the human OTF3 to chromosome 6p21.3 ] p22 and OTF3L to 12p13

Cytogenet Cell Genet

New type of POU domain in germ line-specifi c protein Oct-4

Nature

A POUdomain transcription factor in early stem cells and germ cells of the mammalian embryo

Nature

Analysis of Oct-4 expression and ploidy in individual human blastomeres

Mol Hum Reprod

Oct-4 expression in inner cell mass and trophectoderm of human blastocysts

Mol Hum Reprod

Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry

Cancer

Human embryonic genes re-expressed in cancer cells

Oncogene