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Biomedical subjects

D Corcoran

Publications and source records attributed to D Corcoran.

At least 19 recordsLinked to original sources
PubMed1999

Overexpression of insulin-like growth factor II (IGFII) in ZR-75-1 human breast cancer cells: higher threshold levels of receptor (IGFIR) are required for a proliferative response than for effects on specific gene expression.

Previous transfection experiments using a zinc-inducible expression vector have shown that overexpression of insulin-like growth factor II (IGFII) in MCF7 human breast cancer cells can reduce dependence on oestrogen for cell growth in vitro (DALY RJ, HARRIS WH, WANG DY, DARBRE PD. (1991) Cell Growth Differentiation 2, 457-464.). Parallel transfections now performed into another oestrogen-dependent human breast cancer cell line (ZR-75-1) yielded three clones of transfected ZR-75-1 cells that produced levels of zinc-inducible IGFII mRNA and secreted mature IGFII protein similar to those found in the transfected MCF7 cells. However, unlike in MCF7 cells, no resulting effects were found on cell growth in the ZR-75-1 clones, even though the ZR-75-1 clones possessed receptors capable of binding 125I-IGFI and showed a growth response to exogenously added IGFII. Medium conditioned by the ZR-75-1 clones could stimulate growth of untransfected MCF7 cells, indicating that the secreted IGFII protein was bioactive. Furthermore, zinc-induced IGFII was capable of increasing both pS2 mRNA levels and CAT activity from a transiently transfected AP1-CAT gene in the ZR-75-1 clones. Constitutive co-overexpression of the protein processing enzyme PC2 resulted in reduced levels of large forms of zinc-inducible IGFII, but zinc treatment still produced no effect on cell growth rate. Finally, however, constitutive co-overexpression of the type I IGF receptor (IGFIR) did result in zinc-inducible increased basal cell growth and reduced dependence on oestrogen for cell growth. These results demonstrate that while overexpression of IGFII per se was sufficient to deregulate MCF7 cell growth, the ZR-75-1 cells are limited in their proliferative response by their intrinsic receptor levels. However, although the proliferative response was limited, molecular responses (expression of pS2 and AP1-CAT) were not limited, indicating that different cellular responses can have different threshold receptor level requirements.

Breast Neoplasms↗
PubMed1998

A novel oestrogen-regulated gene in human breast cancer cells identified by differential display.

Screening by differential display of oestrogen-sensitive MCF7 human breast cancer cells grown in the short-term (6 days) and long-term (70 weeks) absence of oestrogen has led to the identification of a new oestrogen-regulated mRNA. The cDNA isolated by differential display has 100% homology from nucleotides 615 to 859 of the published sequence for the mRNA for human megakaryocyte CD63 antigen but has a 3' tail extended by 23 nucleotides. Northern blotting has confirmed that this mRNA is regulated by oestrogen in both MCF7 and T47D human breast cancer cell lines.

Antigens, CD↗
PubMed1997

Technology: evolution or revolution--changing times.

Technology is changing the way work in a department is processed, often leading to greater efficiency and cost savings over time. How nurses engage in the process of business reengineering may help to determine the agency's competitive edge. This article discusses the process and the use of computer technology in the perioperative area.

Diffusion of Innovation↗
PubMed1996

Increased autocrine production of insulin-like growth factor II (IGF-II) alters serum sensitivity of MCF-7 human breast cancer cell proliferation.

Regulation of the growth of breast cancer cells is the result of a complex interaction between steroid hormones and growth factors, and in particular of oestrogen and insulin-like growth factors (IGF). Alteration of any one mitogenic component can affect the cell response to other pathways. Previous work has shown that increased autocrine production of IGF-II from a transfected inducible expression vector can result in reduced oestrogen sensitivity of growth of MCF-7 human breast cancer cells. This report describes alterations to non-oestrogen regulated pathways of cell growth following enhanced IGF-II expression in these transfected MI7 cells. Serum sensitivity of cell growth in the absence of oestrogen was found to differ between MI7 and untransfected MCF-7 cells, in that growth of MI7 but not MCF-7 cells was strongly inhibited by high serum levels. Increased serum had no effect on levels of IGF-II mRNA, IGFIR, IGFBP4 mRNA, or IGFBP secreted in MI7 cells. However, growth inhibition by serum in MI7 cells could be overcome by increasing levels of IGF-II in the serum or by removal of IGFBP onto polycarbonate membranes. Thus, the growth inhibition by serum in MI7 cells is concluded to result from the increased levels of IGFBP added with higher serum. This would support an inhibitory role for IGFBP on growth of breast cancer cells when cell growth is being driven by IGF pathways in the absence of oestrogen, and would suggest that cellular sensitivity to such factors can depend on levels of endogenous IGF production.

Breast Neoplasms↗
PubMed1996

3,4,3',4'-Tetrachlorobiphenyl acts as an estrogen in vitro and in vivo.

Polychlorinated biphenyls (PCBs) are one of the most widespread, persistent man-made products in the ecosystem giving rise to serious environmental contamination and potential hazard to health. The PCBs, in common with other compounds such as the dioxins, have been shown to exert some biological actions mediated through the aryl hydrocarbon receptor. Evidence for interaction of PCBs with other nuclear receptors has been sparse. Here we present evidence that 3,4,3',4'-tetrachlorobiphenyl (TCB) (PCB77), a PCB with high toxicity and significant bioaccumulation, can act as an estrogen with actions mediated through the estrogen receptor. Evidence is presented from multiple assay systems including 1) ligand binding to estrogen receptor in a competitive binding assay, 2) ligand ability to induce estrogen receptor binding to DNA, 3) ligand regulation of gene expression from a transfected exogenous (ERE-tk-CAT) or an endogenous (pS2) estrogen-regulated gene, 4) ligand regulation of cell growth in estrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1, and 5) ligand activity in the immature mouse uterine weight bioassay in vivo. These results demonstrate that TCB (PCB77) can be included in the increasing list of environmental pollutants that possess the ability to mimic estrogen action and be termed an environmental estrogen. Since the concentrations of TCB used here (10(-9) M; 292 ng/liter) are not incompatible with levels of PCB/TCB found in human tissues, these results may have physiological relevance. Use of multiple approaches to study estrogenic action demonstrates that one congener can act as both an agonist and antagonist of estrogen action and that the magnitude of these effects can alter according to the molecular environment.

Animals↗
PubMed1991

In vitro modulation of cellular localization of milk fat globule membrane antigens in human breast carcinomas.

Alterations in the cellular localization of cell surface components such as the milk fat globule membrane are a common feature of breast carcinomas and relate to the differentiation of a tumour. This study has examined the potential modulation of such components. A group of carcinomas were cultured with and without insulin and/or hydrocortisone and the site of staining for milk fat globule membrane, as detected by the antibodies HMFG 1, HMFG 2, and NCRC 11, was assessed using light microscopic and electron microscopic immunohistochemistry. Modulation of localization, with a shift from cytoplasmic vesicle labelling to submembraneous vesicles/cell surface labelling and intracytoplasmic luminal labelling, was observed in 5 of 14 moderately differentiated and 8 of 11 poorly differentiated carcinomas. Two well differentiated carcinomas continued to show peripheral labelling; three poorly differentiated carcinomas showed no change from cytoplasmic labelling only; and the other carcinomas exhibited heterogeneous localization, making any change difficult to assess. Insulin was required for any change to be observed and it is suggested that this has an effect on the mechanisms for intracellular transport of membrane and secretory proteins.

Antigens, Neoplasm↗
PubMed1990

Ultrastructural localization of milk fat globule membrane antigens in human breast carcinomas.

The localization of milk fat globule membrane components has been assessed using post-fixation immunoelectron microscopy with three different antibodies for a group of breast carcinomas of different type and histological differentiation. For well differentiated carcinomas localization was in relation to the cell membrane, with polarization being evident in a proportion of cases. Moderately differentiated carcinomas showed a combined picture of cell membrane, vesicular, and intracytoplasmic luminal localization. The latter is a feature of infiltrating lobular carcinomas. Poorly differentiated carcinomas exhibited vesicular labelling throughout the cytoplasm, with no cell membrane localization. No labelling was seen over endoplasmic reticulum. It is proposed that carcinomas exhibit defects in intracellular transport of milk fat globule membrane components resulting in failure of expression at the cell surface and accumulation of vesicles within the cytoplasm, the extent of change relating to tumour differentiation.

Antigens, Neoplasm↗
PubMed1990

Post embedding immunoelectron microscopy of human breast cancer: a comparison of three acrylic resins.

The suitability of three acrylic resins for the immunoelectron microscopical localization of cell surface and cytoskeletal antigens in surgically excised, immersion fixed human breast cancer, using an immunogold system, has been assessed. Good localization of milk fat globule membrane was achieved with LR White, LR Gold and Lowicryl K11M, although the embedding schedule for LR White had to be modified. The best results were achieved with Lowicryl K11M. Only scanty labelling of actin and cytokeratin was seen in LR White embedded tissue, whereas there was clear localization in LR Gold and Lowicryl K11M embedded samples. Tubulin and alpha-actinin was detected at low level in tissues in the low temperature embedding resins, but not in LR White embedded samples. The morphology of the latter was poorer, and there was greater variability in ultrastructure and labelling. Of the two low temperature embedding resins, Lowicryl K11M gave slightly better results. However, the advantages could be outweighed by the problem incurred in achieving the low temperatures, and by poorer handling properties than LR Gold.

Acrylic Resins↗
PubMed1988

Comparison of human monocytes isolated by elutriation and adherence suggests that heterogeneity may reflect a continuum of maturation/activation states.

Monocytes are heterogeneous both in terms of physical properties and in their functional capacity. Isolation of monocytes from peripheral blood may perturb the observed heterogeneity for purified cell preparations. To explore this possibility we examined monocytes prepared by two techniques, counter-flow centrifugation elutriation (CCE) and fibronectin adherence, in terms of cell-surface molecule expression and several physical properties. Although such cells would be expected to represent dissimilar cross-sections of the total monocyte population, they were found to have similar cell-surface antigenic profiles. Observed differences in levels of expression of several molecules (CR1, CR3 and the antigen recognized by LP9 antibody) were found to be a temperature-related phenomenon. These results indicate that monocytes are not divisible into 'subpopulations' on the basis of cell-surface molecule expression and suggest that heterogeneity of monocytes may reflect the presence in the circulation of a continuum of maturational/activation states.

Antibodies, Monoclonal↗
PubMed1978

The primary structure of the nonpolar segment of bovine cytochrome b5.

The primary structure of the membrane bound segment of amphipathic bovine liver microsomal cytochrome b5 has been determined. This 43 residue nonpolar polypeptide is present at the COOH terminus of cytochrome b5. The sequence was obtained by automated sequence analysis and carboxypeptidase digestions. The sequence obtained is: Ile-Thr-Lys-Pro-Ser-Glu-Ser-Ile-Ile-Thr-Ile-Asp-Ser-Asn-Pro-Ser-Trp-Trp-Thr-Asn-Trp-Leu-Ile-Pro-Ala-Ile-Ser-Ala-Leu-Phe-Val-Ala-Leu-Ile-Tyr-His-Leu-Tyr-Thr-Ser-Glu-Asn. Conformational analysis using predictive algorithms is presented along with circular dichroism data on the peptide bound to phospholipid vesicles.

Amino Acid Sequence↗
PubMed1975

Isolation and structure of a cross-linked tripeptide from calf bone collagen.

A cross-linked tripeptide has been isolated from alkaline hydrolysates of NaB3H4-reduced calf bone collagen. The peptide contains dihydroxylysinonorleucine, the most abundant cross-link in bone collagen, and it has a single N-terminal proline and a single C-terminal valine. These amino acids are in peptide linkage with the cross-link, in a trans configuration with respect to the secondary amine.

Animals↗
PubMed1974

Purification and properties of rat liver microsomal stearyl coenzyme A desaturase.

The terminal enzyme of the NADH-dependent stearyl coenzyme A desaturase system has been isolated from rat liver microsomes. This desaturase is a single polypeptide of 53,000 daltons containing 62% nonpolar amino-acid residues and one atom of non-heme iron. The purified protein forms high molecular weight aggregates that can be dispersed by detergent procedures. Desaturase activity requires NADH, stearyl coenzyme A, oxygen, lipid, and the three enzymes, cytochorme b(5) reductase (EC 1.6.2.2), cytochrome b(5), and desaturase. Cytochrome b(5) is the direct electron donor to the desaturase, which appears to utilize the iron in the oxidation-reduction sequence during desaturation of stearyl coenzyme A.

Animals↗