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At least 19 recordsLinked to original sources
PubMed2006

[Cancer-protecting genes (tumor-suppressor genes)].

Tumor-suppressor genes protect against the development of cancer. The prototypical tumor-suppressor gene is one that controls G1 to S progression in the cell cycle. However, genes that are involved in DNA-repair or induction of apoptosis also protect against the development of cancer. More generally speaking, tumor-suppressor genes either prevent the introduction of somatic mutations or the amplification of the population of somatic cells carrying mutations. Well-known tumor-suppressor genes that also give rise to inherited cancer disorders are described in the review.

Apoptosis↗
PubMed2005

[Cloning tumor-related genes and tumor suppressor genes in glioma with polymerase chain reaction-based subtractive hybridization].

BACKGROUND & OBJECTIVE: Glioma is a common tumor in central nervous system with no specific clinical therapy. Its pathogenesis is unclear. This study was to clone tumor-related genes and tumor suppressor genes in glioma with polymerase chain reaction (PCR)-based subtractive hybridization, and to explore the molecular biological mechanism of tumorigenesis of glioma. METHODS: mRNA was isolated from a sample of human glioma, and reversely transcribed into cDNA. PCR-based subtractive hybridization was used to clone tumor-related genes and tumor suppressor genes from it. RESULTS: In tumor-related candidate gene group, phospho-protein enriched in astrocytes of 15 (PEA15) and homology of acid fibroblast growth factor (aFGF) were picked up. Whereas, in tumor suppressor gene group, interferon-induced protein 17 and ndr2 were picked up. ndr2 was widely expressed in normal brain tissue, but absent in glioma tissue. CONCLUSION: ndr2 gene is a candidate tumor suppressor gene, and may play a role in tumorigenesis of glioma.

Apoptosis Regulatory Proteins↗
PubMedDate not supplied

[Tumor suppressor genes with special emphasis on the APC tumor suppressor gene].

Tumor suppressor genes play a central role in the genesis and progression of human cancers. Genetic alterations of tumor suppressor genes have been found in a variety of hereditary and nonhereditary cancers. Persons that carry a hereditary mutation in tumor suppressor genes are strongly predisposed to one or more kinds of cancer. This review brings current developments in the field of tumor suppressor genes. Special emphasis is dedicated to recently discovered tumor suppressor gene APC (adenomatous polyposis coli) whose mutations are responsible for familial adenomatous polyposis (FAP). The known mutations of the APC gene are described. The role of the APC gene in tumor development, as well as the possibility for presymptomatic genetic testing is also discussed in the paper.

Genes, APC↗
PubMed1999

Exclusion of Leu1 and Leu2 genes as tumor suppressor genes in 13q14.3-deleted B-CLL.

The chromosomal region 13q14.3 is frequently deleted in B cell chronic lymphocytic leukemia (B-CLL) and it is supposed that a tumor suppressor gene, involved in this leukemogenesis, is located in this area. The first exons of two genes, Leu1 and Leu2, mapped in a minimally deleted 13q14.3 region, are systematically lost in B-CLL sharing a 13q14.3 deletion. These two genes have been proposed as strong tumor suppressor gene candidates. However, in a study on 15 13q14.3 deleted B-CLL, we found three patients in which this critical region was not involved. Because of these results and that no mutations were detected on the two genes in a previous study, we think that Leu1 and Leu2 can be excluded as tumor suppressor genes.

CD5 Antigens↗
PubMed1995

[Mechanisms for inactivation of tumor suppressor genes].

Tumor suppressor genes are inactivated by various mechanisms. Since a mutant allele of a tumor suppressor gene is recessive for cellular malignant transformation, mutation is heritable and germ line mutations of tumor suppressor genes such as retinoblastoma gene and p53 gene are well characterized. In the process of loss-of-function of a tumor suppressor gene, chromosome type of mutations are often involved, which results in tumor specific loss of heterozygosity (LOH) on a specific chromosome. Somatic mutations of the p53 gene in a variety of tumors were extensively studied and a huge data base is now available. Mutation spectra of the p53 gene in various tumors are different each other and to be used as a molecular indicator of carcinogens involved in each type of tumor.

Gene Expression Regulation, Neoplastic↗
PubMed2004

Gene therapy progress and prospects: cancer gene therapy using tumour suppressor genes.

Targeting tumour suppressor gene pathways is an attractive therapeutic strategy in cancer. Since the first clinical trial took place in 1996, at least 20 other trials have investigated the possibility of restoring p53 function, either alone or in combination with chemotherapy, but with limited success. Other recent clinical trials have sought to harness abnormalities in the p53 pathway to permit tumour-selective replication of adenoviral vectors such as dl1520 (Onyx-015). Other tumour suppressor genes, such as retinoblastoma (Rb) and PTEN (phosphatase, tensin homologue, deleted on chromosome 10), are the targets for imminent clinical trials, while microarray technologies are revealing multiple new genes that are potential targets for future gene therapy.

Gene Targeting↗
PubMed2002

Childhood cerebellar hemangioblastoma does not predict germline or somatic mutations in the von Hippel-Lindau tumor suppressor gene.

Tumor suppressor gene "knockout" models would predict that children who present with hemangioblastoma are likely to harbor germline mutation of the von Hippel-Lindau gene. We screened 6 pediatric patients with cerebellar hemangioblastoma for germline or somatic mutations of the von Hippel-Lindau gene. Two had prior clinical manifestations of von Hippel-Lindau disease and, as expected, had germline von Hippel-Lindau gene mutations. Four children with solitary hemangioblastoma did not have a detectable germline deletion, rearrangement, or point mutation in their von Hippel-Lindau gene, and tumor specimens in 3 of these 4 showed no somatic von Hippel-Lindau allelic loss. Solitary cerebellar hemangioblastoma in children does not predict a germline or somatic mutation in the von Hippel-Lindau tumor suppressor gene. The tumorigenesis of hemangioblastoma in younger patients may differ from that in adults, and may involve a molecular process unrelated to the von Hippel-Lindau tumor suppressor pathway.

Adolescent↗
PubMed2000

The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.

We used overlapping and nested homozygous deletions, contig building, genomic sequencing, and physical and transcript mapping to further define a approximately 630-kb lung cancer homozygous deletion region harboring one or more tumor suppressor genes (TSGs) on chromosome 3p21.3. This location was identified through somatic genetic mapping in tumors, cancer cell lines, and premalignant lesions of the lung and breast, including the discovery of several homozygous deletions. The combination of molecular manual methods and computational predictions permitted us to detect, isolate, characterize, and annotate a set of 25 genes that likely constitute the complete set of protein-coding genes residing in this approximately 630-kb sequence. A subset of 19 of these genes was found within the deleted overlap region of approximately 370-kb. This region was further subdivided by a nesting 200-kb breast cancer homozygous deletion into two gene sets: 8 genes lying in the proximal approximately 120-kb segment and 11 genes lying in the distal approximately 250-kb segment. These 19 genes were analyzed extensively by computational methods and were tested by manual methods for loss of expression and mutations in lung cancers to identify candidate TSGs from within this group. Four genes showed loss-of-expression or reduced mRNA levels in non-small cell lung cancer (CACNA2D2/alpha2delta-2, SEMA3B [formerly SEMA(V), BLU, and HYAL1] or small cell lung cancer (SEMA3B, BLU, and HYAL1) cell lines. We found six of the genes to have two or more amino acid sequence-altering mutations including BLU, NPRL2/Gene21, FUS1, HYAL1, FUS2, and SEMA3B. However, none of the 19 genes tested for mutation showed a frequent (>10%) mutation rate in lung cancer samples. This led us to exclude several of the genes in the region as classical tumor suppressors for sporadic lung cancer. On the other hand, the putative lung cancer TSG in this location may either be inactivated by tumor-acquired promoter hypermethylation or belong to the novel class of haploinsufficient genes that predispose to cancer in a hemizygous (+/-) state but do not show a second mutation in the remaining wild-type allele in the tumor. We discuss the data in the context of novel and classic cancer gene models as applied to lung carcinogenesis. Further functional testing of the critical genes by gene transfer and gene disruption strategies should permit the identification of the putative lung cancer TSG(s), LUCA, Analysis of the approximately 630-kb sequence also provides an opportunity to probe and understand the genomic structure, evolution, and functional organization of this relatively gene-rich region.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

The deleted in colorectal cancer (DCC) gene: a candidate tumour suppressor gene encoding a cell surface protein with similarity to neural cell adhesion molecules.

Chromosome 18q is among the regions thought to harbour a tumour suppressor gene(s) that is frequently inactivated by LOH during the development of several cancer types, including those of the gastrointestinal tract. In addition, colorectal cancers with 18q LOH have been shown to have a more aggressive clinical behaviour than those without 18q LOH. A candidate tumour suppressor gene from 18q, called DCC, has been identified. The DCC gene is contained within the common region of LOH on 18q, its expression is markedly decreased or absent in the majority of colorectal cancers and cell lines and somatic mutations within the DCC gene have been identified in a subset of cases. Thus, DCC represents the strongest candidate tumour suppressor gene on 18q. At present, however, many questions remain regarding the mechanisms underlying the inactivation of DCC and its decreased expression in cancers. The predicted structural similarity of DCC to the NCAMs suggests that it may function through cell-cell and/or cell-extracellular matrix interactions; however, little is known regarding the specific cellular function(s) of DCC. Many reports have detailed the alterations in phenotype observed in cancer cells, including changes in cell morphology and tissue architecture, loss of differentiated phenotype, decreased cell adhesion and aggregation, increased motility and invasive behaviour. These altered properties are likely to account in part for the invasive and metastatic properties of cancer cells in the patient. It is hoped that further studies will identify the means by which DCC inactivation may contribute to the altered growth properties of advanced cancer cells.

Alternative Splicing↗
PubMed2002

Molecular cloning and characterization of ST7R (ST7-like, ST7L) on human chromosome 1p13, a novel gene homologous to tumor suppressor gene ST7 on human chromosome 7q31.

ST7 is a tumor suppressor gene, which is clustered with WNT2 gene in human chromosome 7q31 region. WNT2 gene is homologous to WNT2B gene. WNT2B gene encodes two isoforms due to alternative splicing of alternative promoter type. WNT2 and WNT2B isoform 2 (WNT2B2) are positive regulators of the WNT - beta-catenin - TCF signaling pathway. Here, a novel ST7-related gene ST7R (ST7-like, ST7L) was identified by using bioinformatics, and ST7R cDNAs were isolated by using cDNA-PCR. ST7R gene encoded 575-amino-acid polypeptide with leucine zipper domain and 3 tyrosine-phosphorylation sites. Human ST7R was homologous to human ST7 (72.1% total-amino-acid identity) and Drosophila CG3634 (56.8% total-amino-acid identity). Leucine zipper domain was unique to ST7R. Tyr 268 and Tyr 441 of ST7R were conserved in ST7 and CG3634. ST7R-homologous domains (S7H1, S7H2, and S7H3) were conserved among ST7R, ST7, and CG3634. ST7R gene consisted of at least 15 exons, and four ST7R isoforms were transcribed due to alternative splicing. ST7R and WNT2B genes, located in human chromosome 1p13 region, were clustered in tail-to-tail manner with an interval of less than 5.0-kb. ST7R-WNT2B and ST7-WNT2 gene clusters might be generated due to duplication of an ancestral gene cluster. Because allelic loss or rearrangements of human chromosome 1p13 region are reported in breast cancer, germ cell tumors, squamous cell carcinoma of head and neck, non-small cell lung cancer, gastrointestinal stromal/smooth muscle tumors (GIST), meningioma, melanoma, acute megakaryoblastic leukemia (M7), and Kaposi's sarcoma, ST7R might be a novel tumor suppressor gene on human chromosome 1p13.

Alternative Splicing↗
PubMedDate not supplied

Tumor suppressor genes.

Tumor suppressor genes are negative regulators of cell growth. When their normal function is compromised, absence of their inhibitory effects can lead to unrestrained cell cycling and growth. Strong evidence now confirms that loss of proper function of these genes is a common occurrence leading to cancer. Their failure can be caused by alterations in the gene DNA or malfunction of their protein products. The recent extraordinary accumulation of knowledge about these genes reveals that normal carcinogenesis represents breakdown of normal regulatory processes.

Cell Transformation, Neoplastic↗
PubMed1995

[Structure and function of tumor suppressor genes].

Tumor suppressor genes encode molecules involved in cell adhesion, cytoplasmic signal transduction, transcriptional regulation and DNA repair. Recent studies have shown that p53 and WT1 regulate the cell cycle by altering the expression of genes involved in controlling the activity of cyclin/CDK complexes. By contrast, RB regulates the expression of genes that mediate cell cycle progression from the G1 to S phase and its activity is negatively regulated by cyclin/CDK. Recent progress in this field is summarized in the light of cell cycle control.

Animals↗
PubMed2004

Expression in bladder transitional cell carcinoma by real-time quantitative reverse transcription polymerase chain reaction array of 65 genes at the tumor suppressor locus 9q34.1-2: identification of 5 candidates tumor suppressor genes.

Frequent deletions on 9q34.1-2 were reported in bladder transitional cell carcinoma. High deletion mapping studies delimited a critical interval between markers D9S61 and D9S66, which is highly susceptible to contain a tumor suppressor gene. Expression level of the 65 genes localized in this region was analyzed by real-time quantitative RT-PCR, comparing tumor to normal urothelium. Five genes exhibited a significantly reduced expression level: C9orf9, KIAA0625, ABL1, LAMC3 and KIAA1857-netrin-G2, which exhibited the most significant downregulation (p=0.0007). KIAA1857-netrin-G2 belongs to the netrins and might then be a tumor suppressor gene in bladder cancer, as netrin1 receptor DCC has been implicated in tumorigenesis.

Carcinoma, Transitional Cell↗
PubMed2000

[Gene therapy with tumor suppressor gene p53 and(or) p16 on the nude mice models of NSCLC in vivo].

OBJECTIVE: To investigate the effect of tumor suppressor gene p53 and(or) p16 treatment on the nude mice models of non-small cell lung cancer (NSCLC). METHODS: Nude mice were injected subcutaneously with NSCLC cell line A549. 25 nude mice were randomly divided into 5 groups (control, SA, p53 gene, p16 gene, p53 + p16 genes), p53 and(or) p16 genes mediated by stearylamine/DOPE (SA liposome) were injected intratumorally alone or jointly. The size of tumor and survival period of nude mice were measured after treatment. RESULTS: p53 and(or) p16 genes can obviously inhibit the growth of tumor. The difference was significant between control and treated groups, among which the combined p53 and p16 genes enhance the inhibiting effect more markedly. The survival period of tumor-bearing nude mice was prolonged after transfecting p53 gene or p16 gene alone, p53 and p16 genes jointly can prolong the survival period significantly. CONCLUSIONS: Tumor suppressor gene p53 and(or) p16 in the replacement therapy of NSCLC are of potential clinical significance. The combination of p53 and p16 gene may have a greater antitumoral effect in vivo.

Animals↗
PubMed1995

Transgenic mouse models for tumour-suppressor genes.

Tumour-suppressor genes are negative regulators of cell division and growth. Over the past decade, multiple, distinct tumour-suppressor genes have been identified and cloned. In recent years, the ability to specifically manipulate the mouse genome via overexpression, underexpression or deletion of genes using transgenic expression systems and embryonic stem cell (ES) technology has led to the identification and definition of the precise function of several tumour suppressor genes in vivo. Included in this group are mice with mutations in the p53 and retinoblastoma (Rb) genes. p53 Mutant mice are highly susceptible to tumour development and will serve as excellent models to understand the aetiology and pathology of several human cancers. In contrast to the role of the Rb gene in human retinoblastomas, mice heterozygous for a mutant Rb allele do not develop retinoblastoma, but develop pituitary tumours instead. Similar ES cell technology has been used to generate alpha-inhibin deficient mice. Inhibin-deficient mice develop gonadal and adrenal tumours with nearly 100% penetrance. These studies have identified inhibin as a novel secreted tumour suppressor. In the future, many of the unidentified functions of tumour-suppressor genes can be tested using this powerful in vivo assay system.

Animals↗
PubMed2005

Establishment of a cell line from a malignant rhabdoid tumor of the liver lacking the function of two tumor suppressor genes, hSNF5/INI1 and p16.

Malignant rhabdoid tumors (MRT) of the liver are rare. A few liver MRT cell lines have been established but none has been characterized in detail. Here we describe a new MRT cell line from the liver, which is designated MP-MRT-AN, and describe it in detail. Immunohistochemical assays detected the expression of vimentin and cytokeratin but they were negative for neurofilament, desmin, alpha-smooth muscle actin, alpha-sarcomeric actin, and smooth muscle myosin heavy chains SM1 and SM2. RT-PCR assays revealed that this cell line did not express smooth muscle myosin heavy chain isoforms or MyoD1. No aberration was identified in 22q by G-banded analysis; however, the hSNF5/INI1 gene, a suppressor gene of MRT that maps to 22q11.2, was homozygously deleted from exons 1 to 5 in this cell line. Furthermore, the expression of another tumor suppressor gene, p16 (CDKN2A), was not detected by RT-PCR. This raises the possibility that the aggressive phenotype of malignant rhabdoid tumors is caused by the loss of two or more tumor suppressor genes.

Animals↗
PubMed2005

Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing.

To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-expressing T-cell lymphomas. p16 gene was epigenetically silenced in all but one of the 10 malignant T-cell lines examined, p15 gene silenced in roughly half of the lines, and p14 was the least frequently affected. Extensive methylation of the p16 promoter was seen in six out of 10 cutaneous T-cell lymphoma patient samples and corresponded with lack of p16 protein expression in the cases examined. Treatment of cultured T-cells with the DNA methyltransferase inhibitor, 5-aza-2-deoxy-cytidine, resulted in reversal of the p16 gene silencing. However, expression of p16 protein was delayed in relationship to p16 promoter demethylation and required up to 3 weeks to occur, seemingly reflecting late activation of the p16 gene. These findings indicate that epigenetic silencing affects in T-cell malignancies, often simultaneously, several tumor suppressor genes that impact on key cell functions. The observed differential silencing of p16 and p14, and to a lesser degree p15 gene, indicates that the silencing is governed by precise, promoter region-specific mechanisms. The study provides also further rationale for treatment of at least some types of T-cell lymphomas with DNA methyltransferase inhibitors to target the epigenetically silenced tumor suppressor genes.

Adult↗