RESUMO
In this report, we describe the cloning of the coding region of human WIG-1 cDNA. The human 8 and 6 kb WIG-1 transcripts are both upregulated following ionizing irradiation of the human colon cancer cell lines HCT116 and LoVo which have wild type TP53 but not in DLD1 cells that lack wild type TP53. Basal levels of both WIG-1 transcripts were detected in human adult brain, kidney, and testis, but not in fetal brain, heart, pancreas, adrenal gland, fetal liver, and small intestine. FISH analysis mapped the human WIG-1 gene to 3q26.3. Investigation of squamous cell carcinomas of the lung by Southern blot and semiquantitative RT-PCR analysis showed amplification in combination with increased expression of WIG-1 in 1/7 tumors and increased expression in a further two cases.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas de Transporte/genética , Cromossomos Humanos Par 3/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/genética , Proteínas Nucleares/genética , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Southern Blotting , Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/metabolismo , Células Cultivadas/efeitos da radiação , Mapeamento Cromossômico , Clonagem Molecular , Primers do DNA/química , Proteínas de Ligação a DNA/metabolismo , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/metabolismo , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , RNA/metabolismo , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Chromosome 6 deletions are common in human neoplasms including gliomas. In order to study the frequency and identify commonly deleted regions of chromosome 6 in astrocytomas, 159 tumours (106 glioblastomas, 39 anaplastic astrocytomas and 14 astrocytomas malignancy grade II) were analysed using 31 microsatellite markers that span the chromosome. Ninety-five per cent of cases with allelic losses had losses affecting 6q. Allelic losses were infrequent in astrocytomas malignancy grade II (14%) but more usual in anaplastic astrocytomas (38%) and glioblastomas (37%). Evidence for clonal heterogeneity in the astrocytomas and anaplastic astrocytomas was frequently observed (i.e. co-existence of subpopulations with and without chromosome 6 deletions). Clonal heterogeneity was less common in glioblastomas. Five commonly deleted regions were identified on 6q. These observations suggest that a number of tumour suppressor genes are located on 6q and that these genes may be involved in the progression of astrocytic tumours.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 6 , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Centrômero , DNA Satélite/genética , Progressão da Doença , Humanos , TelômeroRESUMO
Wild type p53 expressed from a temperature-sensitive (ts p53) construct induces both G1 cell cycle arrest and apoptosis in the p53-negative J3D mouse T lymphoma line (Wang et al., 1995). Using differential display analysis, we have identified one new p53-induced gene, wig-1 (for wild type p53-induced gene 1), whose 7.6 kb and 2.2 kb transcripts are upregulated in ts p53-transfected J3D cells following induction of wild type p53 expression by temperature shift to 32 degrees C. The wig-1 transcripts were also induced in irradiated NIH3T3 and p21-/- fibroblasts but not in irradiated p53-/- fibroblasts. Whole body gamma irradiation caused induction of both wig-1 transcripts in mouse brain, testis, kidney, spleen and lung. A basal wig-1 expression was detected in brain, testis and kidney. The WIG-1 protein contains three zinc finger motifs and a putative nuclear localization signal.
