Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer.

Aims And Background: The Wnt/beta-catenin signaling pathway is one of the main carcinogenic mechanisms in human malignancies including prostate cancer. Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. In addition, alterations of the DVL1 gene have been reported in breast and cervical cancer.

Up-regulation of CC chemokine, CCL3L1, and receptors, CCR3, CCR5 in human glioblastoma that promotes cell growth.

Human CC ligand 3-like protein 1 (CCL3L1), a member of the CC chemokine family, that induces MCP1 and RANTES, exhibits a variety of proinflammatory activities including chemotaxis, and functional and proliferative activation of leukocytes, lymphocytes and macrophages. Its signal is transmitted through transmembrane receptors, CC chemokine receptors, CCR1, CCR3 and CCR5. To examine gene expression of chemokine, CCL3L1, and its receptors, CCR1, CCR3 and CCR5, we analyzed tumor tissues from 21 patients with several types of primary gliomas.

Characterization of liver-cirrhosis nodules by analysis of gene-expression profiles and patterns of allelic loss.

To disclose genetic mechanisms involved in development or progression of hepatocellular carcinoma (HCC), we used a genome-wide cDNA microarray consisting of 8,448 genes to compare gene-expression profiles among 12 liver-cirrhosis nodules (LCNs) and five specimens of HCC excised from a single patient and carefully prepared by laser-capture microdissection (LCM). The expression patterns enabled us to identify 72 genes that were frequently upregulated and 57 that were downregulated specifically in the LCN specimens as compared to the HCCs. We also documented upregulation of 31 genes and downregulation of seven others in both HCC and LCN tissues.

Gene expression patterns as marker for 5-year postoperative prognosis of primary breast cancers.

Purpose: To establish the novel prognostic markers for breast cancer, gene expression profile was examined genome-wide.

Methods: We used cDNA microarray consisting of 18,432 human genes to compare genome-wide expression profiles of eight primary breast cancers, four from patients who died of breast cancer within 5 years after surgery (5D group) and four who survived disease-free for more than 5 years (5S group).

Results: We identified 21 genes whose expression was greater in tumors from the 5D group than in 5S tumors, and 23 with higher expression in the 5S group than in the 5D group.

Amplification, up-regulation and over-expression of C3G (CRK SH3 domain-binding guanine nucleotide-releasing factor) in non-small cell lung cancers.

The Ras-CRK-Rap1 cellular signal-transduction system is regulated by guanine nucleotide exchange factors (GEFs). Transcription of C3G on chromosome 9q34 and a key member of the GEF gene family is activated by the CRK-adaptor protein; the C3G product is a CRK SH3 domain-binding guanine nucleotide-releasing factor. We document here the amplification of C3G in five of 18 primary non-small cell lung cancers examined and its increased expression in 18 of 28 tumors in comparison to corresponding non-cancerous lung tissues.

Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray.

Estrogen receptor (ER) status is an essential determinant of clinical and biological behavior of human breast cancers. While ER-positive breast cancers respond well to adjuvant hormone therapy, ER-negative tumors are generally resistant. To date, no attempts have succeeded in finding molecular markers for classifying ER-negative breast cancers with respect to postoperative prognosis.

Upregulation and overexpression of human X-box binding protein 1 (hXBP-1) gene in primary breast cancers.

Background: Human X-box binding protein 1 (hXBP-1) is a transcription factor essential for hepatocyte growth as well as for plasma cell differentiation. hXBP-1 also binds to cis-elements of human T cell leukemia virus and human major histocompatibility complex genes. In order to clarify the role of XBP-1 in breast cancer, here we investigated the expression of XBP-1 in 11 primary breast cancers and 5 breast cancer cell lines.

Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma.

The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways. Wnt signaling activates the gene encoding DVL-1; the latter suppresses beta-catenin by promoting its degradation through enhanced inactivation of glycogen-synthase-kinase 3 (GSK3). Here we demonstrate increased expression of DVL-1 mRNA in over two thirds of primary cervical squamous cell cancers (11 of 15 cases) when compared to corresponding non-cancerous uterine squamous cell tissues.

Amplification, up-regulation and over-expression of DVL-1, the human counterpart of the Drosophila disheveled gene, in primary breast cancers.

Wnt proteins form a family of highly conserved, secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Wnt genes and Wnt signaling are also implicated in cancer. It has been shown that Wnt proteins bind to receptors of the frizzled family on the cell surface.

Universal fluorescent labeling (UFL) method for automated microsatellite analysis.

We have devised a novel method for automated microsatellite analysis using "universal" fluorescent labeling. This system is based on polymerase chain reactions driven by sequence-specific primers and a reporter primer labeled with a fluorescent dye at its 5' end. The forward sequence-specific primer is designed with a tag region bearing no homology to any human genomic sequence.

Correlation of allelic losses and clinicopathological factors in 504 primary breast cancers.

Background: We have defined 18 chromosomal regions in which allelic losses were frequent among breast cancers. We examined whether specific allelic losses might correlate with any clinicopathological factors.

Methods: We tested DNA from matched normal and tumor tissues for loss of heterozygosity (LOH) at 18 microsatellite loci from a cohort of 504 patients who had undergone surgery for breast cancer.