Involvement of C12orf32 overexpression in breast carcinogenesis.

Through genome-wide gene expression profile analysis of breast cancer, we identified a gene, chromosome 12 open reading frame 32 (C12orf32), to be involved in mammary carcinogenesis. Semiquantitative RT-PCR and Northern blot analysis confirmed C12orf32 overexpression in breast cancer cells and its almost undetectable level of expression in normal human tissues. Immunocytochemical staining analysis using breast cancer cell lines revealed a cell cycle-dependent subcellular localization of endogenous C12orf32 protein.

Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells.

To investigate the molecular mechanism of mammary carcinogenesis and identify novel molecular targets for breast cancer therapy, we analyzed genome-wide gene expression profiles of 81 clinical breast cancer samples. Here, we report the critical role of LGN/GPSM2 (Leu-Gly-Asn repeat-enriched protein/G-protein signaling modulator 2) in the growth of breast cancer cells. Semiquantitative RT-PCR and Northern blot analyses confirmed upregulation of LGN/GPSM2 in a large proportion of breast cancers.

Involvement of RQCD1 overexpression, a novel cancer-testis antigen, in the Akt pathway in breast cancer cells.

We here report identification and characterization of required for cell differentiation 1 homolog (RQCD1) as a potential therapeutic target for breast cancer. Gene-expression profiling analysis of breast cancer cells, semi-quantitative RT-PCR, Northern blotting and Western blotting confirmed RQCD1 to be frequently up-regulated in breast cancer specimens and breast cancer cell lines. On the other hand, its expression was very weak or hardly detectable in normal human tissues except testis, indicating this molecule to be a novel cancer-testis antigen.

Involvement of G-patch domain containing 2 overexpression in breast carcinogenesis.

Through analysis of the detailed genome-wide gene expression profiles of 81 breast tumors, we identified a novel gene, G-patch domain containing 2 (GPATCH2), that was overexpressed in the great majority of breast cancer cases. Treatment of breast cancer cells MCF-7 and T47D with siRNA against GPATCH2 effectively suppressed its expression, and resulted in the growth suppression of cancer cells, suggesting its essential role in breast cancer cell growth. We found an interaction of GPATCH2 protein with hPrp43, an RNA-dependent ATPase.

Radioimmunotherapy of solid tumors targeting a cell-surface protein, FZD10: therapeutic efficacy largely depends on radiosensitivity.

Objective: Frizzled homolog 10 (FZD10) is expressed at high levels on the cell surface of almost all synovial sarcoma tissues, but is absent in most normal organs. In a previous study, yttrium-90 ((90)Y)-labeled anti-FZD10 antibody (MAb 92-13) showed considerable therapeutic efficacy in synovial sarcoma cell-bearing mice. The purpose of the present study was to elucidate the factors associated with this therapeutic efficacy of (90)Y-MAb 92-13.

Inverse correlation of the up-regulation of FZD10 expression and the activation of beta-catenin in synchronous colorectal tumors.

We investigated the immunohistochemical expression patterns of Frizzled homolog 10 (FZD10), a cell-surface receptor for molecules in the Wnt pathway, in tissue samples derived from 104 patients with colorectal cancers (CRCs). There was no immunoreactivity for FZD10 in normal colonic mucosa, and only tumor cells in polyps and CRC tissues showed spotted immunostaining patterns in apical sides of the cytoplasm. In metastatic liver lesions, tumor cells showed cytoplasmic immunostaining similar to primary lesions, whereas normal liver parenchyma showed almost no immunostaining.

Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10.

We previously reported Frizzled homolog 10 (FZD10), a member of the Frizzled family, to be a promising therapeutic target for synovial sarcomas. In this report, we established a murine monoclonal antibody (MAb), namely, MAb 92-13 that had specific binding activity against native FZD10 product expressed in synovial sarcoma cell lines. Subsequent immunohistochemical analyses with the MAb 92-13 confirmed an absence or hardly detectable level of FZD10 protein in any normal human organs.

Molecular target therapy for synovial sarcoma.

Although the specific chromosomal translocation and fusion gene SYT-SSX in synovial sarcoma (SS) has been identified, the molecular mechanism of its tumorigenesis is largely unknown. Recent gene-expression profiles of soft-tissue tumors using cDNA microarray demonstrated that SS has the distinct gene-expression pattern from other sarcomas and has a similar pattern to that of malignant peripheral nerve sheath tumors, indicating that the origin of SS is likely to be the neural crest cells. Through this analysis, several genes were found to be specifically upregulated in SS and considered to play an important role in the proliferation of SS cells.

pp32/ I-1(PP2A) negatively regulates the Raf-1/MEK/ERK pathway.

In this study, we focus on the potential interaction of pp32/I-1(PP2A) (pp32) with the Raf-MEK-ERK signaling pathway. We show that overexpressed pp32 suppresses Raf-1 activation, thereby downregulating the level of ERK activation. This suppression of Raf-1 requires the C-terminal half of pp32.

Therapeutic potential of antibodies against FZD 10, a cell-surface protein, for synovial sarcomas.

Genome-wide expression profiling revealed overexpression of the gene encoding frizzled homologue 10 (FZD 10), a cell-surface receptor for molecules in the Wnt pathway, as a potential contributor to synovial sarcomas (SS). Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors and cell lines examined but absent in most normal organs or in some cancers arising in other tissues. Treatment of human SS cells with small-interfering RNA (siRNA) to FZD 10 decreased the amount of its product and suppressed growth of SS cells.

The oncoprotein I-2PP2A/SET negatively regulates the MEK/ERK pathway and cell proliferation.

I-2PP2A/SET, the translocation breakpoint-encoded protein expressed in acute undifferentiated leukemia, was identified as an inhibitor of protein phosphatase 2A (PP2A). Induction of exogenous I-2PP2A/SET at a ratio of 1:1 to the endogenous protein resulted in suppression of cell proliferation. In contrast, siRNA-mediated depletion of I-2PP2A/SET resulted in enhanced cell proliferation.