PubMed Health⌕ Search

Biomedical subjects

S Umhauer

Publications and source records attributed to S Umhauer.

3 recordsLinked to original sources

Gap junctional intercellular communication and connexin 43 expression in ovarian carcinoma.

OBJECTIVES: Gap junctions, which are composed of subunits termed connexins, are plasma membrane channels that link the interior of adjacent cells and permit cells to directly exchange small molecules and ions. Loss or dysfunction of gap junctions appears to be important in allowing cancer cells to escape growth regulation. In a previous study we showed that human ovarian surface epithelial cells exhibited extensive gap junctions and expression of connexin 43. These were nearly absent in human ovarian adenocarcinoma cell lines. To ensure that this variation was not artificially produced by culturing techniques, this study evaluated gap junctions and connexin 43 expressions in normal ovaries and in ovarian adenocarcinomas. STUDY DESIGN: Specimens of normal ovaries and ovarian adenocarcinomas were obtained at the time of surgery and flash-frozen in liquid nitrogen. Connexin 43 immunostaining was performed on all specimens. RESULTS: Among the 11 normal ovaries an average of 59% of the surface epithelium stained positively for connexin 43. In contrast, among the 10 ovarian adenocarcinomas only 19% of each specimen stained positively for connexin 43 (P =.01). CONCLUSION: Similar to our studies on human ovarian surface epithelial cells and ovarian adenocarcinoma cell lines, surgical specimens of normal ovary exhibited extensive connexin 43 expression, whereas connexin 43 expression was nearly absent in ovarian adenocarcinomas. It thus appears that the previously reported loss of gap junctions and connexin 43 was actually associated with a neoplastic process, rather than being artificially induced in the laboratory.

Connexin 43↗

Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro.

Gap junctional intercellular communication (GJIC) and the expression of gap junction proteins (connexins) are frequently decreased in neoplastic cells and have been increased by cAMP and retinoids. GJIC and connexin expression were investigated in early passage normal human ovarian surface epithelial (HOSE) cells, human ovarian adenocarcinoma cell lines (CaOV-3, NIH:OVCAR-3, SK-OV-3 and SW626) and surgical specimens of human serous cystadenocarcinomas. We hypothesized that GJIC and connexin expression would be decreased in neoplastic cells and would be increased by cAMP and retinoic acid. Cultured HOSE cells exhibited extensive fluorescent dye-coupling and connexin43 (Cx43) expression; other connexins were not detected. The ovarian adenocarcinoma cell lines had little dye-coupling or connexin expression. Deletions and rearrangements of the Cx43 gene were not detected by Southern blotting in the carcinoma lines. N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate and all-trans-retinoic acid inhibited cell proliferation, but did not enhance GJIC or Cx43 expression. Surface epithelial cells of benign ovaries expressed Cx43, but this expression was barely detectable in ovarian serous cystadenocarcinomas. Thus, normal HOSE cells had extensive GJIC and Cx43 expression whereas ovarian carcinoma cells had less and cAMP and retinoic acid did not change these, although both agents inhibited cell growth.

Adenocarcinoma↗

Interaction of tacrine and velnacrine with neocortical synaptosomal membranes: relevance to Alzheimer's disease.

The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes. Electron paramagnetic resonance employing a protein-specific spin label was used to monitor this interaction. Analogous to their effects in erythrocyte membranes [Butterfield and Rangachari (1992) Biochem. Biophys. Res. Commun. 185: 596-603], in the present studies both agents decreased segmental motion of spin labeled synaptosomal membrane proteins, consistent with increased cytoskeletal protein-protein interactions (0.001 < P < 0.005), and tacrine was more potent than velnacrine. These results are discussed with possible relevance to molecular actions of the agents and molecular alterations in Alzheimer's disease.

Alzheimer Disease↗