Biomedical subjects

L Hornez

Publications and source records attributed to L Hornez.

27 records · Page 2Linked to original sources

PubMed1989

Secretion of transferrin by human breast cancer cells.

Transferrin (Tf), the major iron-binding protein in the plasma of vertebrate species is an essential growth factor for cells in serum-free media and appears to be involved in the regulation of growth and differentiation of human tissues. We report here that human breast cancer cells secrete a factor immunologically similar to Tf. The secretion of Tf by the hormone-responsive cell-line MCF-7 is stimulated by 17 beta-estradiol and reduced by the antiestrogen 4-hydroxy tamoxifen. These data suggest that Tf secreted by breast cancer cells may be an additional autocrine growth factor confering selective advantages to rapidly proliferating breast cancer cells and perhaps permit tumor cell growth in poorly vascularized areas.

Breast Neoplasms↗

PubMed1988

Assay of GCDFP-15 by ELISA: an available method for in vitro studies of functional differentiation in human breast cancer.

An enzyme-linked immunosorbent assay (ELISA) was applied to a light protein, isolated from human breast cyst fluid (BCF) termed "gross cystic disease fluid protein - 15 Kda" (GCDFP-15), a potential differentiation marker in in vitro human breast cancer studies. The detection limits of this procedure, performed in microtiter plates, were 0.5 to 250 ng/well corresponding to 10 ng/ml to 5 micrograms/ml of sample or antigen solution. Possible cross-reaction with various antigens, especially those found in culture media, were investigated. The correlation coefficient between enzymoassay and radioimmunoassay was 0.978. The results showed that quantification of GCDFP-15 by ELISA is a specific and highly sensitive method. This procedure may be of interest in in vitro studies on the functional differentiation of breast cancer cells.

Apolipoproteins↗

PubMed1988

Characterization of catecholestrogen membrane binding sites in estrogen receptor positive and negative human breast cancer cell-lines.

A specific membrane-binding of an estradiol metabolite, the catecholestrogen (CE) 2 hydroxyestrone (2OH-E1), was demonstrated in two receptor-positive (MCF7 and VHB1) and one receptor-negative (MDA-MB-231) human mammary carcinoma cell lines. The three cell lines were found to be able to synthesise and inactivate CE. Solubilization of membrane bound CE results in a high molecular weight component whose specificity differs from that of the classical estrogen receptor. Apparent dissociation constants were 6-10. 10(-9) M and binding capacities were higher in the receptor-positive cell lines than in the receptor-negative one. Since CE are susceptible to rapid degradation, the presence of such a site may be relevant in the protection and concentration of 2OH-E1 which has been shown to have "in vitro" anti-estrogenic properties in MCF7 breast tumor cells.

Binding Sites↗

PubMed1986

Further characterization of the light breast cyst fluid protein, GCDFP-15.

A light protein of breast cyst fluid from women with gross cystic disease, termed GCDFP-15 in the literature, has been investigated. This light protein was purified by preparative electrophoresis on sodium dodecyl sulfate polyacrylamide gel. Its isoelectric point has been determined as 3.75 and its molecular weight has been estimated at 17 400. The light protein was a glycoprotein containing about 163 amino acid residues; the glucidic fraction corresponded to 11% of the molecular weight. The N-terminal amino acid was blocked and the C-terminal amino acid was determined as valine. Antisera raised against this light protein have proved to be specific. In the literature, there is evidence suggesting that apocrine secretion is of prime importance in conditioning the biochemical composition of breast cyst fluid. Further information is needed to substantiate the hypothesis that in gross cystic disease the apocrine epithelium itself or some of its functional aspects are associated with the risk of neoplasia. The physicochemical characterization of the breast cyst fluid protein can contribute to the study of its biosynthesis and provide a better understanding of the physiopathology of gross cystic disease and its relationship to breast carcinoma.

Amino Acids↗

PubMedDate not supplied

Prognostic value of tumoral sialyltransferase expression and circulating E-selectin concentrations in node-negative breast cancer patients.

AIMS AND BACKGROUND: A crucial step in the metastatic process is the interaction between the endothelial molecule E-selectin and its tumoral ligands sialyl-Lewis- and sialyl-Lewis. Sialyltranferases are involved in the biosynthesis of these ligands. The aim of this study was to assess the prognostic value of tumoral sialyltransferase expression and of circulating soluble E-selectin (sE-selectin) in node-negative breast cancer patients. METHODS: Using a multiplex RT-PCR method, we measured the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I and ST3Gal II) in tumors of 135 surgically treated node-negative breast cancer patients. Circulating sE-selectin concentrations were measured by an ELISA method prior to surgery. We also analyzed tumor size, histoprognostic grading and steroid hormone receptor status. RESULTS: The median follow-up was 7.5 years. Expression of estrogen receptors was associated with a good prognosis for relapse-free survival in univariate analysis. A high ST3Gal III/ST6Gal I ratio and a high sE-selectin concentration were associated with a bad prognosis for relapse-free survival and overall survival in univariate and multivariate analysis. CONCLUSION: In the present study, tumoral sialyltransferase expression and circulating sE-selectin concentrations had prognostic value in patients with node-negative breast cancer. This result provides further evidence for the important role of these agents in the metastatic process.

Adult↗

PubMedDate not supplied

Distribution and prognostic value of the fibroblast growth factor-2 low-affinity binding sites in human breast cancer.

We performed a competitive binding study with 125I-labelled FGF (fibroblast growth factor)-2 and unlabelled FGF-2 in an unselected series of two hundred and thirty human primary breast cancers. One hundred and ninety-two breast cancer biopsies possessed FGF-2 low-affinity binding sites (FGF-2 LABS). The median dissociation constant was 2.4 nM (range, 1.03-18) and the median concentration of membrane protein was 6187.5 fmol/mg (range, 831-90,000). FGF-2 LABS concentrations were positively correlated to the progesterone receptor level. Cox univariate analyses showed that the FGF-2 LABS (> or = upper quartile) was associated to a longer overall survival (p = 0.05; RR = 0.042); node involvement, estrogen receptor progesterone receptor and histoprognostic grading were also prognostic. In Cox multivariate analyses, only the progesterone receptor, estrogen receptor, node involvement and FGF-2 LABS were prognostic factors; the FGF-2 LABS were associated with a longer overall survival (p = 0.033; RR = 0.068). The present study showed that FGF-2 LABS have only a limited role as a prognostic factor in breast cancer.

Adult↗

PubMedDate not supplied

Beta-adrenergic receptors in human breast cancer: identification, characterization and correlation with progesterone and estradiol receptors.

Besides the variety of other cellular processes in which beta-adrenergic compounds have been involved, their effect on the second messenger cAMP is thought to be related to the growth and differentiation of malignant cells. Because beta-adrenergic receptor could be an easy target for a new combination treatment, we attempted to identify and characterize adrenergic receptor in breast tumor and sought for correlations with estradiol and progesterone receptors. Using L[3H]-dihydroalprenolol, a potent beta-adrenergic antagonist, we demonstrated in human breast tumor the presence of beta-adrenergic receptors with high affinity (Kd 1-3 nM) as shown by Scatchard analyses. Natural and synthetic agonists and antagonists inhibited the [3H] DHA binding, mainly in the order of beta 2-subtype potency. We verified that these receptors were normally coupled with G-protein. A slight correlation was shown between adrenergic and progesterone receptors, and no correlation between adrenergic and estrogen receptors. The presence of specific beta-adrenergic receptors functionally coupled with G protein incited us to study their physiological regulation, since it is tempting to speculate that circulating or locally released catecholamines or other natural compounds may participate in the process of growth and differentiation of the mammary gland through adrenergic receptors.

Biomarkers, Tumor↗

PubMedDate not supplied

C-myc overexpression, c-mil, c-myb expression in a breast tumor cell line. Effects of estrogen and antiestrogen.

In breast tumor cell lines, c-myc amplification is frequently associated with estrogen unresponsiveness. We, however, succeeded in characterizing an estrogen-responsive cell line VHB1 derived from a duct cell carcinoma, which exhibits c-myc amplification and overexpression. We therefore studied the effects of estrogen and antiestrogen on c-myc expression in this particular cell line. We also investigated these effects on the expression of c-mil and c-myb oncogenes, also expressed but not amplified in VHB1 cells. Short-(1 h) and long-(72 h) term stimulations were performed. Our experiments showed that estradiol (E2 10(-8) M) was still able to stimulate c-myc expression equally either after short or long-term treatment. In the same way, the antiestrogen 4-hydroxytamoxifen equally decreased c-myc expression but the reversal effect of E2 after long-term antiestrogen treatment was more pronounced than after short-term treatment. The effects of E2 and 4-OH Tam on the expression of the not-amplified c-mil and c-myb oncogenes were stronger than those observed on c-myc expression; however, the E2 reversal effect was identical either after short or long-term antiestrogen treatment. Our results may enlighten some aspects of the complex action of some of the early- and late-growth regulated genes in breast cancer.

Blotting, Northern↗

PubMedDate not supplied

Influence of cAMP on E-cadherin expression and cell surface heparan sulfate proteoglycan synthesis in human breast cancer cells.

The growth of MCF-7 and MDA-MB-231 human breast cancer cells was inhibited by treatment with dibutyryl cAMP (dBcAMP, 10(-4) M). The effects on E-cadherin expression and cell surface associated heparan sulfate proteoglycans (HSPG) synthesis, both implicated in cell adhesion, were investigated. dBcAMP was demonstrated to increase E-cadherin expression in the E-cadherin positive MCF-7 cells. However, in the E-cadherin negative MDA-MB-231 cells, the treatment did not induce expression of this cell adhesion molecule. Furthermore, in the two cell lines, an increase of the [35S] Na2SO4 incorporation into the cell surface sulfated PG was observed subsequently to dBcAMP treatment. Interestingly, the proportion of cell surface HSPG was also enhanced by this treatment. Taken together, these results demonstrate that the decrease of the proliferation observed in the human breast cancer cells after dBcAMP treatment is associated with an increase in the cell-cell and cell-matrix interactions. This suggests that the metastatic process which involves lack of cohesiveness and migration of the cells may probably be counteracted by cAMP in the human breast cancer cells.

Breast Neoplasms↗