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Visualization of cancer initiating cell in the vascular niche utilized with transcriptional activity of PSF1

ABSTRACT: Identification of cancer stem/initiating cells (CSCs/CICs) by a specific marker is useful for diagnosis and therapy of cancer. We have determined that PSF1 which plays a role in DNA replication in lower species is strongly expressed in wide range of normal stem cell population. Here, utilizing the transcriptional activity of PSF1 promoter in tumor cell xenograft model, we show that PSF1high cancer cells display malignant features including high proliferating activity, serial transplantation potential, and metastatic ability those are used for criteria of CSCs/CICs. PSF1high cancer cells localize in perivascular region and genetically display ES cell like signature. Silencing of PSF1 by RNAi inhibited growth of cancer cells mediated by disruption of DNA synthesis and chromosomal segregation. These suggested that PSF1 is a possible maker and a molecular target of CSCs/CICs.

ORGANISM(S): Mus musculus

PROVIDER: GSE17112 | GEO | 2010/03/31

SECONDARY ACCESSION(S): PRJNA119797

REPOSITORIES: GEO

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Visualization of cancer initiating cell in the vascular niche utilized with transcriptional activity of PSF1

Project description:Identification of cancer stem/initiating cells (CSCs/CICs) by a specific marker is useful for diagnosis and therapy of cancer. We have determined that PSF1 which plays a role in DNA replication in lower species is strongly expressed in wide range of normal stem cell population. Here, utilizing the transcriptional activity of PSF1 promoter in tumor cell xenograft model, we show that PSF1high cancer cells display malignant features including high proliferating activity, serial transplantation potential, and metastatic ability those are used for criteria of CSCs/CICs. PSF1high cancer cells localize in perivascular region and genetically display ES cell like signature. Silencing of PSF1 by RNAi inhibited growth of cancer cells mediated by disruption of DNA synthesis and chromosomal segregation. These suggested that PSF1 is a possible maker and a molecular target of CSCs/CICs. We have cloned the mouse PSF1 promoter gene and established lung carcinoma (lewis lung carcinoma: LLC) and colon cancer (colon26) cell lines stably expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of PSF1 promoter (LLC- and colon-PSF1P-EGFP, respectively). Mouse xenograft tumor cells were dissociated and sorted into PSF1 low and high expression cells by FACS. We sought whether PSF1 high expression cells possess embryonic stem cells-like signature.

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