January 2012 Volume 40 Issue 1

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International Journal of Molecular Medicine

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International Journal of Oncology

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Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Biomedical Reports, founded in 2013, is a monthly, peer-reviewed journal, dedicated to publishing research across all fields of biology and medicine, including pharmacology, pathology, gene therapy, genetics, microbiology, neurosciences, infectious diseases, molecular cardiology and molecular surgery. The Journal provides a home for original research, case reports and review articles and is now abstracted in Scopus (Elsevier) Dec 2017.

Molecular and Clinical Oncology

Molecular and Clinical Oncology is a monthly medical journal in the field of oncology that covers a wide range of original research, while offering a rapid publication process. The articles comprising each issue are carefully selected, peer-reviewed and revised to provide a wide variety of high-quality scientific research. Articles published in Molecular and Clinical Oncology are listed in various databases, such as PubMed and PubMed Central.

World Academy of Sciences Journal

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International Journal of Functional Nutrition

International Journal of Functional Nutrition is an international journal devoted to Functional Nutrition.

International Journal of Epigenetics

An International Open Access Journal Devoted to Epigenetics Research and Treatment.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January 2012 Volume 40 Issue 1

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Article

Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3/4 and SOX2

Authors:
- Hajime Iida
- Mitsuhiro Suzuki
- Ryo Goitsuka
- Hikaru Ueno
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Affiliations: Department of Biochemistry, University of Occupational and Environmental Health, Fukuoka, Japan, Department of Biochemistry, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka, Japan
Published online on: September 22, 2011 https://doi.org/10.3892/ijo.2011.1207
Pages: 71-79

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Abstract

CD133 has been recognized as a specific cell surface marker for cancer stem cells in various tumors, although its biological functions and transcriptional regulation remain unclear. We found that the CD133 expression level was up-regulated in the lung cancer cell lines N417, H358, and A549, when these cell lines were cultured under hypoxic conditions. Among the five promoters (P1-P5) of human CD133 gene loci, P1 promoter was most strongly associated with hypoxia-induced promoter activity of CD133 gene expression. The P1 promoter possesses several cis-regulatory elements, including RUNT, GATA, ETS, OCT, SRY, and CREB-binding sites. A series of deletion and base substitution mutants of the P1 promoter revealed that OCT- and SRY-binding sites are important for hypoxia-induced promoter activity. The chromatin immunoprecipitation assay further confirmed the direct binding of Octamer biding transcription factor 3/4 (OCT4) and/or SRY-box containing gene 2 (SOX2) to the P1 promoter region of CD133 gene loci. In addition, the enhancement of both OCT4 and SOX2 expression by the α subunit of hypoxia-inducible factors (HIF1α and HIF2α) was required for hypoxia-induced CD133 expression. Knockdown of OCT4 or SOX2 expression in N417 cells with stabilized HIF1α and/or HIF2α abolished CD133P1 activity, while ectopic OCT4 or SOX2 expression triggers CD133P1 activity in the absence of HIF1α or HIF2α. Thus, in the hypoxic conditions, OCT4 and SOX2, both of which are induced by HIF1α/HIF2α. promote CD133 expression in the lung cancer cells via their direct interaction with the P1 promoter.