Involvement of NANOG upregulation in malignant progression of human cells.

Previously, we isolated cell lines that display various degrees of transformed phenotypes from a single-cell population of human diploid fibroblasts (RB) containing a large deletion (13q14-22) in one copy of chromosome 13. They included a cell line transfected with SV40 early genes (RBSV), an immortalized cell line (RBI), an anchorage-independent cell line (RBS), and a tumorigenic cell line (RBT). Here, we analyzed gene expression profiles in these cell lines and showed that expression of some fibroblast-specified or mesenchyme-specified genes were downregulated, and those of stem cell-specified genes, including NANOG, were upregulated during malignant progression.

A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF.

The protein p14ARF is a known tumor suppressor protein controlling cell proliferation and survival, which mainly localizes in nucleoli. However, the regulatory mechanisms that govern its activity or expression remain unclear. Here, we report that a novel proapoptotic nucleolar protein, PANO, modulates the expression and activity of p14ARF in HeLa cells.

Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors.

Neuroendocrine tumors in the lung fall into four categories: typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC), in ascending order of malignancy. The drs gene was originally isolated as a suppressor against v-src transformation and was shown to induce apoptosis in human cancer cells. The expression of drs was markedly downregulated in various human cancer tissues and cell lines.

Downregulation of drs mRNA expression is associated with the progression of adult T-cell leukemia/lymphoma.

Although adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-cell leukemia virus (HTLV-1), many other factors are thought to be required for the progression from indolent ATL to aggressive ATLL. The drs gene was originally isolated as a novel suppressor gene of v-src transformation and was shown to induce apoptosis in human cancer cells. To investigate the involvement of drs downregulation in the progression of ATLL, we examined the expression of drs in smoldering, chronic and aggressive ATLL, and found that drs expression was markedly reduced in clinically aggressive ATLL.

Oleamide derivatives suppress the spontaneous metastasis by inhibiting connexin 26.

We previously reported that overexpressing connexin 26 (Cx26) enhances the spontaneous metastasis of mouse BL6 melanoma cells. In contrast, daily intraperitoneal injections of an oleamide derivative named MI-18 potently inhibits the spontaneous metastasis of BL6 cells. In the present study, we chemically synthesized a novel oleamide derivative named MI-22 and found that it also efficiently suppressed the spontaneous metastasis of BL6 cells.

Down-regulation of ASY/Nogo transcription associated with progression of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human leukemia/lymphoma. Although this disease is initiated by infection with human T-lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long period without aggressive illness, suggesting that other factors may play roles in the progression of ATLL to an aggressive state. However, the mechanism involved in this progression still remains unclear.

A novel apoptotic pathway induced by the drs tumor suppressor gene.

The drs gene was originally isolated as a suppressor against v-src transformation. Expression of drs mRNA was markedly downregulated in a variety of human cancer cell lines and tissues, suggesting that the drs gene acts as a tumor suppressor. In this study, we found that ectopic expression of the Drs protein induced apoptosis in human cancer cell lines.

Expression of Epstein-Barr virus in thyroid carcinoma correlates with tumor progression.

There have been few studies regarding cancer progression from differentiated thyroid carcinoma to the undifferentiated one. To examine the possible involvement of Epstein-Barr virus (EBV) in this progression, 10 papillary carcinomas and 11 undifferentiated carcinomas were subjected to mRNA in situ hybridization, indirect immunofluorescence staining, polymerase chain reaction (PCR), and reverse-transcriptase PCR. mRNA in situ hybridization using a BamHIW probe revealed signals in all of the examined samples, although the signal strength was weaker in the papillary carcinomas than in the undifferentiated carcinomas.

Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.

We have previously shown that ectopic expression of the ASY/Nogo-B gene induced apoptosis in various cancer cell lines. Nogo-A, a splice variant of the ASY, has been reported to have an inhibitory effect on neuronal regeneration in the central nervous system. To investigate the mechanism of ASY-induced apoptosis or inhibition of neuronal regeneration, we cloned a cDNA for the ASY-interacting protein from the human cDNA library using the yeast two-hybrid method, and obtained a cDNA we designated as ASYIP.

Suppression of anchorage-independent growth of human cancer cell lines by the TRIF52/periostin/OSF-2 gene.

In searching for genes that suppress the viral transformation of primary cells, we have isolated a number of TRIF (transcript reduced in F2408) genes that are expressed well in primary rat embryo fibroblasts (REFs) but poorly in spontaneously immortalized rat fibroblast cell lines derived from REFs. One of these genes, TRIF52, is a rat homologue of the mouse protein periostin, which is suspected of being involved in oncogenesis. We found here that periostin mRNA expression is markedly downregulated in a variety of human cancer cell lines and human lung cancer tissues.

Expression of drs mRNA in human lung adenocarcinomas.

The drs gene was originally isolated from a rat primary embryo fibroblast cDNA library as a suppressor gene against v-src transformation. We have previously shown that expression of drs mRNA was markedly reduced in a variety of human cancer cell lines, including those of the colon, bladder, and ovary. Furthermore, introduction of drs cDNA by retrovirus vector into these cancer cell lines caused suppression of anchorage-independent growth without affecting cell proliferation.