Cancer

ARTICULOS
1.ANALYSIS OF TSG101 TUMOUR SUSCEPTIBILITY GENE TRANSCRIPTS IN CERVICAL AND ENDOMETRIAL CANCERS
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Abstract
Carcinoma of the uterine cervix is a common malignancy among women that has been found to show loss of heterozygosity in the chromosome 11p. Recent studies have localized the TSG101 gene in this region, and also demonstrated ahigh frequency of abnormalities of this gene in human breast cancer. To determine the role of the TSG101 gene in the carcinogenesis of cervical and uterine carcinoma, 19 cases of cervical carcinoma and five cases of endometrial carcinoma, as well as nearby non-cancerous tissue from the same patients, and 16 blood samples from healthy persons as normal control were analysed by Southern blot analysisof genomic DNA, reverse transcription of the TSG101 mRNA followed by PCR amplification and sequencing of the products. We found that abnormal transcripts of the TSG101 gene were common both in cancerous or non-cancerous tissues of the uterus and cervix and in normal peripheral mononuclear cells. There was no genomic deletion or rearrangement in spite of the presence of abnormal transcripts, and nodefinite relationship between the abnormal transcripts and HPV infection was found. Although the frequency of abnormal transcripts was higher in cancerous than in non-cancerous tissue, normal peripheral mononuclear cells also had abnormal transcripts. Given these findings, the role of the TSG101 gene as a tumour-suppressor gene should be re-evaluated. Because some aberrant transcripts could befound at the first PCR reaction, we suggest that the aberrant transcripts might be the result of imperfect minor splicesome products.
2.IDENTIFICATION AND CHARACTERIZATION OF E-APC, A NOVEL DROSOPHILA HOMOLOGUE OF THE TUMOUR SUPPRESSOR APC
Abstract
Background: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The productof the APC gene forms a complex with b-catenin, glycogen synthase kinase 3b (GSK-3b) and Axin/ conductin, and induces the degradation of bcatenin.
Results: We have identi®ed a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The EAPC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the15-amino acid repeat, ®ve copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of b-catenin) in vitro, destabilizes intracellular bcatenin, and suppresses b-catenin/TCF-regulated transcription in APCÿ/ÿ colon cancer cells. The EAPC mRNA is ubiquitously expressed throughout all developmental stages inDrosophila.
Conclusion: Our ®ndings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.
3. REDUCTION OF CHROMIUM(VI) AND ITS RELATIONSHIP TO CARCINOGENESIS
Abstract
Although Cr(VI)-containing compounds are well-documented carcinogens, their mechanism of action is still not well understood. Recentstudies have suggested that reduction of Cr(VI) to its lower oxidation states and related free-radical reactions play an important role in carcinogenesis. This article summarizes recent studies on (1) the reduction of Cr(VI) by ascorbate, diol- and thiol-containing molecules, certain flavoenzymes, cell organelles, intact cells, and whole animals; (2) free-radical production with emphasis on hydroxyradical generation via Fenton or Haber-Weiss type reactions; and (3) freeradical-induced cellular damage, such as DNA strand breaks, hydroxylation of 2'deoxyguanosine, and activation of nuclear transcription factor B.
4. NEOPLASTIC TRANSFORMATION OF NORMAL RAT EMBRYO FIBROBLASTS BY A MUTATED P53 AND AN ACTIVATED RAS ONCOGENE INDUCES PARATHYROID HORMONE-RELATED PEPTIDE GENE EXPRESSION
Abstract...