PubMed · 6788142
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J C Nicholls, P A Smith. 1981-04-11. How far down the duodenum?. https://doi.org/10.1136/bmj.282.6271.1223
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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.
Several dozen lung epithelial cell lines have been established in culture over the past 20 years from normal lung explants and their spontaneous transformants, and from lung tumors that arose spontaneously or were induced with chemicals, viruses, or oncogenic transgenes. To provide information from which to choose appropriate lines for investigating problems in lung cell biology and pulmonary neoplasia, this review describes the origins of these lines and some of their characteristics. These include growth, morphology, tumorigenicity, ability to metastasize, xenobiotic metabolism, mutational status, signal transducing activities, cytogenetics, ability to form domes, and electric conductance. In addition to collecting this information in a single place for the first time, we describe previously unpublished apoptosis features of some of these lines. An increasing number of investigations are beginning to use these lines and this review contains references into 1997.
BACKGROUND: Variant CD44 splice products, especially CD44 variant 6 (CD44v6), are expressed on activated lymphocytes and tumor cells. The soluble forms of CD44 standard (CD44s) and CD44v6 are present in the serum of normal individuals. The aim of the current study was to evaluate the concentrations and the prognostic potential of soluble CD44s and CD44v6 in patients with pancreatic carcinoma. METHODS: The serum CD44s and CD44v6 levels were determined quantitatively by enzyme-linked immunosorbent assay. The molecular mass of CD44v6 isoforms was determined by immunoprecipitation and Western blot analysis. CD44 mRNAs were analyzed by reverse transcriptase polymerase chain reaction followed by exon specific analysis. RESULTS: Both serum CD44s and serum CD44v6 were significantly reduced in patients with pancreatic carcinoma (n = 93, P < 0.001 and P < 0.00005). The median survival in the group with CD44v6 serum concentrations below 100 ng/mL was significantly decreased compared with that in the group with serum concentrations higher than 100 ng/mL (6.7 vs. 15.1 months, P < 0.0005). The isoforms containing soluble CD44v6 (sCD44v6) that were detected in the sera of pancreatic carcinoma patients showed molecular masses comparable to the sCD44v6 isoforms detected in the supernatant of lymphocytes activated by phorbol myestral acetate, whereas the sCD44v6 isoforms detected in the supernatant of pancreatic carcinoma cell lines exhibited higher molecular masses. CONCLUSIONS: These results suggest that serum CD44v6 is significantly reduced in pancreatic carcinoma patients and could serve as a good prognostic marker for patients with this disease.