PubMed · 7440122
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T J Robinson. 1980. Hepatic dysfunction associated with hypernephroma.. https://pubmed.ncbi.nlm.nih.gov/7440122/
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The G12 subfamily of heterotrimeric G proteins, comprised of the alpha-subunits Galpha12 and Galpha13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we sought to identify molecular targets of Galpha12. Here we show a specific interaction between the G12 subfamily and the cytoplasmic tails of several members of the cadherin family of cell-surface adhesion proteins. Galpha12 or Galpha13 binding causes dissociation of the transcriptional activator beta-catenin from cadherins. Furthermore, in cells lacking the adenomatous polyposis coli protein required for beta-catenin degradation, expression of mutationally activated Galpha12 or Galpha13 causes an increase in beta-catenin-mediated transcriptional activation. These findings provide a potential molecular mechanism for the previously reported cellular transforming ability of the G12 subfamily and reveal a link between heterotrimeric G proteins and cellular processes controlling growth and differentiation.
BACKGROUND: The aim of this study was to compare the results of DNA image cytometry using single-cell preparations to measurements on thin histological slides of the same tumor block, in order to find the most sensitive way for detecting aneuploidy. METHODS: Twenty-three cases of prostatic adenocarcinoma were investigated by image cytometry to assess the DNA content of tumor cell nuclei. The histograms obtained by section measurements were corrected using the algorithms of Haroske et al. [Zentralbl Pathol 139: 407-417, 1994] and McCready and Papadimitriou [Anal Quant Cytol 5:117-123, 1983]. The basis for recalculation was an exact determination of the thickness of the sections used. RESULTS: Out of the 23 cases investigated, 10 tumors were diploid in the single-cell preparations, whereas 13 were classified as nondiploid. After tissue section measurements and mathematical correction of the histograms, five originally diploid histograms showed an additional aneuploid stem line. This was also the case in 8 of the 13 originally aneuploid cases. CONCLUSIONS: Tissue section measurements turned out to be more sensitive in detecting aneuploid tumor cell populations compared to measurements of cytospins of disintegrated tissue. As aneuploidy provides important prognostic information, this more sensitive means of ploidy determination could be of use in prostatic adenocarcinoma, and should especially be used in cases showing diploid histograms in single-cell cytometry.
Drug-induced DNA demethylation in normal human cells and inherited localized hypomethylation in mitogen-stimulated lymphocytes from patients with a rare recessive disease (ICF: immunodeficiency, centromeric region instability, facial anomalies) are associated with karyotypic instability. This chromosomal recombination is targeted to heterochromatin in the vicinity of the centromere (pericentromeric region) of human chromosome 1. Pericentromeric rearrangements in this chromosome as well as overall genomic hypomethylation are frequently observed in many kinds of cancer, including breast adenocarcinoma. We found that almost half of 25 examined breast adenocarcinomas exhibited hypomethylation in satellite 2 DNA, which is located in the long region of heterochromatin adjacent to the centromere of chromosome 1 and is normally highly methylated. One of the 19 examined non-malignant breast tissues displaying fibrocystic changes was similarly hypomethylated in this satellite DNA. We also looked at an opposing type of methylation alteration in these cancers, namely, hypermethylation in a tumor-suppressor gene region that is frequently hypermethylated in breast cancers. We found that increased methylation in the E-cadherin promoter region and decreased methylation in satellite 2 DNA were often present in the same breast cancers. While hypermethylation in certain tumor-suppressor gene regions may favor tumorigenesis by repressing transcription, demethylation of other DNA sequences may predispose to cancer-promoting chromosomal re-arrangements.