A mammary‐derived growth inhibitor (MDGI) related 70 kDa antigen identified in nuclei of mammary epithelial cells

Abstract

The aim of the present study was to investigate the expression of the mammary-derived growth inhibitor (MDGI) and the subcellular localization of MDGI-related antigens in bovine mammary glands. Cell-free translation of poly(A+) = RNA, immunoprecipitation with rabbit anti-MDGI-antibodies, and estimation of the relative contents of MDGI by a radioimmunoassay in mammary tissue of different functional states revealed that the 13 kDa MDGI was dramatically increased in terminally differentiated mammary tissue compared with the proliferating tissue from pregnant animals. To address the question of tissue localization, polyclonal anti-MDGI antibodies and antibodies directed against a synthetic peptide corresponding to residues 69 to 78 of MDGI were used. Western blotting of tissue fractions revealed the cytosolic and microsomal localization of MDGI. Additionally, both types of antibodies detected a 70-kDa antigen in the nuclear fraction of differentiated mammary glands. Salt extraction and DNase I digestion of isolated nuclei, as well as chromatin purification, indicated an association of the 70-kDa antigen with the chromatin. By means of the immunogold technique, MDGI-related antigens were localized within euchromatic nuclear regions of epithelial cells in the intact differentiated mammary gland. The immunostaining was markedly diminished in the proliferating tissue. This finding raises the possibility that MDGI and the 70-kDa antigen influence cell proliferation by acting on gene expression within the nuclei of mammary glands.

Expression of DA11, a neuronal-injury-induced fatty acid binding protein, coincides with axon growth and neuronal differentiation during central nervous system development

“…The conservation of critical amino acids involved in FFAs binding and cellular differentiation in DA11 (Ross, 1993;Yang et al, 1994;Veerkamp and Maatman, 1995;De León et al, 1996) suggests a mechanism of action similar to other FABPs (Muller et al, 1989;Yang et al, 1994). For example, in vitro experiments have shown that BLBP antiserum inhibits neuronal and glial differentiation (Feng et al, 1994).…”

“…Neonatal brain synthesizes lipid at higher rates than adult brain (Bourre, 1980), and the cellular concentration of FFAs or retinoids is significantly higher than that in the adult brain (Bazan et al, 1971;Maden and Holder, 1991). Cellular FFAs mediate a number of processes such as enzyme inhibition (Bass et al, 1984), regulation of cell growth and differentiation (Muller et al, 1989), and induction of the expression of genes associated with lipid metabolism (Distel et al, 1992;Amri et al, 1995). Therefore, the regulation of DA11 expression during CNS development may be triggered in part by the action of its putative ligand in responsive neurons.…”

Cancer risk related to mammary gland structure and development

“…The amino-acid sequence of MDGI and/or the gene encoding it have been sequenced in cattle (Bohmer et al, 1987), rat (Jones et al, 1988), mouse (Treuner et al, 1994;Tweedie and Edwards, 1989), and human heart (Borchers et al, 1990;Huynh et al, 1995). A 70 kDA antigen has been identified in mammary epithelial cells (Muller et al, 1989). The human heart FABP3, that covers an 8-kb region of genomic DNA, is considered to be identical to MDGI and homologue to the bovine MDGI (Phelan et al, 1996).…”

Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1.

“…Results presented in this paper show that ETS2 mRNA and proteins are induced during the early phase of T-cell proliferation, thus enabling us to place c-ets-2 genes along with other "early response genes" such as those encoding ornithine decarboxylase, cyclin, myb, and lymphokine gene products (32 (38), and six growth-arrest-specific genes (39)-also have been shown to be expressed at higher levels in quiescent cells but not in proliferating cells. In contrast to other genes, the protooncogene ETSJ encodes a labile nuclear phosphoprotein with DNA-binding properties (10,13,14), which suggests that this protein may be a regulator rather than a marker of the quiescent state in human T cells.…”