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PMID: 7962070 Published · ppublish English Comparative Study Journal Article

Members of the fatty acid binding protein family are differentiation factors for the mammary gland.

The Journal of cell biology ·Vol. 127 ·No. 4 ·1994-11-00 ·Pages 1097-109

Yang Y, Spitzer E, Kenney N, Zschiesche W, Li M, Kromminga A, Müller T, Spener F, Lezius A, Veerkamp JH

Abstract

Mammary gland development is controlled by systemic hormones and by growth factors that might complement or mediate hormonal action. Peptides that locally signal growth cessation and stimulate differentiation of the developing epithelium have not been described. Here, we report that recombinant and wild-type forms of mammary-derived growth inhibitor (MDGI) and heart-fatty acid binding protein (FABP), which belong to the FABP family, specifically inhibit growth of normal mouse mammary epithelial cells (MEC), while growth of stromal cells is not suppressed. In mammary gland organ culture, inhibition of ductal growth is associated with the appearance of bulbous alveolar end buds and formation of fully developed lobuloalveolar structures. In parallel, MDGI stimulates its own expression and promotes milk protein synthesis. Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures. Furthermore, MDGI suppresses the mitogenic effects of epidermal growth factor, and epidermal growth factor antagonizes the activities of MDGI. Finally, the regulatory properties of MDGI can be fully mimicked by an 11-amino acid sequence, represented in the COOH terminus of MDGI and a subfamily of structurally related FABPs. This peptide does not bind fatty acids. To our knowledge, this is the first report about a growth inhibitor promoting mammary gland differentiation.

MeSH Terms
Amino Acid Sequence Animals Carrier Proteins/antagonists & inhibitors,biosynthesis,physiology Cattle Cell Differentiation/drug effects Cell Division/drug effects Cells, Cultured Conserved Sequence Epithelial Cells Epithelium/drug effects,physiology Fatty Acid Binding Protein 3 Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Fatty Acids/metabolism Female Gene Expression/drug effects Growth Inhibitors/pharmacology Humans Mammary Glands, Animal/cytology,physiology Mice Mice, Inbred BALB C Molecular Sequence Data Neoplasm Proteins Nerve Tissue Proteins Organ Culture Techniques Peptide Biosynthesis Peptides/pharmacology Recombinant Proteins/pharmacology Sequence Homology, Amino Acid Tumor Suppressor Proteins
Chemicals
Carrier Proteins FABP3 protein, human FABP7 protein, human Fabp3 protein, mouse Fabp5 protein, mouse Fabp7 protein, mouse Fatty Acid Binding Protein 3 Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Fatty Acids Growth Inhibitors Neoplasm Proteins Nerve Tissue Proteins Peptides Recombinant Proteins Tumor Suppressor Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yang Y
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Spitzer E
Kenney N
Zschiesche W
Li M
Kromminga A
Müller T
Spener F
Lezius A
Veerkamp J H
References (67)
67 references, click to expand
  1. Hierarchic and cooperative binding of the rat liver nuclear protein C/EBP at the hepatitis B virus enhancer.
    Mol Cell Biol. 1990 Aug;10(8):4427-30 PMID: 2370872
  2. Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids.
    Proc Natl Acad Sci U S A. 1990 Jul;87(14):5543-7 PMID: 2371287
  3. Use of T7 RNA polymerase to direct expression of cloned genes.
    Methods Enzymol. 1990;185:60-89 PMID: 2199796
  4. Intracellular fatty acid trafficking and the role of cytosolic lipid binding proteins.
    Prog Lipid Res. 1989;28(4):245-72 PMID: 2701895
  5. Characteristics of fatty acid-binding proteins and their relation to mammary-derived growth inhibitor.
    Mol Cell Biochem. 1990 Oct 15-Nov 8;98(1-2):57-68 PMID: 2266970
  6. Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis.
    Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):276-80 PMID: 1986376
  7. Signal transduction by interferon-alpha through arachidonic acid metabolism.
    Science. 1991 Jan 11;251(4990):204-7 PMID: 1898993
  8. TNF induces c-fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite.
    EMBO J. 1991 Jan;10(1):109-15 PMID: 1899225
  9. Structural and functional features of different types of cytoplasmic fatty acid-binding proteins.
    Biochim Biophys Acta. 1991 Jan 4;1081(1):1-24 PMID: 1991151
  10. Regulation of mammary epithelial cell growth in mice and rats.
    Endocr Rev. 1990 Nov;11(4):494-523 PMID: 2292240
  11. Overexpression of the cellular retinoic acid binding protein-I (CRABP-I) results in a reduction in differentiation-specific gene expression in F9 teratocarcinoma cells.
    J Cell Biol. 1991 Mar;112(5):965-79 PMID: 1847931
  12. Tissue distribution of cellular retinol-binding protein and cellular retinoic acid-binding protein: use of monospecific antibodies for immunohistochemistry and cRNA for in situ localization of mRNA.
    Methods Enzymol. 1990;189:315-24 PMID: 1963464
  13. Differentiation-promoting effects of mammary-derived growth inhibitor (MDGI) on pluripotent mouse embryonic stem cells.
    Virchows Arch B Cell Pathol Incl Mol Pathol. 1990;59(6):339-42 PMID: 1981402
  14. Hormone-dependent differentiation of mammary gland in vitro.
    Proc Natl Acad Sci U S A. 1965 Aug;54(2):629-34 PMID: 5217449
  15. Whole mammary gland organ culture: selection of appropriate gland.
    In Vitro. 1973 Sep-Oct;9(2):129-33 PMID: 4760586
  16. Epidermal growth factor requirement for development of cultured mammary gland.
    Nature. 1980 May 22;285(5762):250-2 PMID: 6966378
  17. Molecular cloning of DNA complementary to bovine growth hormone mRNA.
    J Biol Chem. 1980 Aug 25;255(16):7521-4 PMID: 6893197
  18. Multiple hormone interactions in the developmental biology of the mammary gland.
    Physiol Rev. 1980 Oct;60(4):1049-106 PMID: 7001510
  19. Tumor promoter 12-O-tetradecanoylphorbol 13-acetate, like epidermal growth factor, stimulates cell proliferation and inhibits differentiation of mouse mammary epithelial cells in culture.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1646-9 PMID: 6300862
  20. Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development.
    J Biol Chem. 1983 Aug 25;258(16):10083-9 PMID: 6411703
  21. Purification of a growth inhibitor for Ehrlich ascites mammary carcinoma cells from bovine mammary gland.
    Exp Cell Res. 1984 Feb;150(2):466-76 PMID: 6363109
  22. Diurnal variation of cytosolic fatty acid-binding protein content and of palmitate oxidation in rat liver and heart.
    J Biol Chem. 1984 Apr 10;259(7):4295-300 PMID: 6538567
  23. Epidermal growth factor receptor levels in mouse mammary glands in various physiological states.
    Endocrinology. 1985 Jul;117(1):405-11 PMID: 2988925
  24. Specific neutralizing antiserum against a polypeptide growth inhibitor for mammary cells purified from bovine mammary gland.
    Biochim Biophys Acta. 1985 Jul 30;846(1):145-54 PMID: 4016153
  25. Adipocyte P2 gene: developmental expression and homology of 5'-flanking sequences among fat cell-specific genes.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3786-90 PMID: 3520554
  26. Bifunctional activity of epidermal growth factor on alpha- and kappa-casein gene expression in rodent mammary glands in vitro.
    Endocrinology. 1986 Sep;119(3):1178-84 PMID: 3525127
  27. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells.
    Proc Natl Acad Sci U S A. 1987 Jan;84(1):136-40 PMID: 3467345
  28. Growth of mammary epithelial cells in breast-cancer biopsies correlates with EGF binding.
    Int J Cancer. 1987 Mar 15;39(3):279-82 PMID: 3493223
  29. Prostaglandin E1 binds to Z protein of rat liver.
    Eur J Biochem. 1987 Feb 2;162(3):615-9 PMID: 3830160
  30. Functional differentiation of virgin mouse mammary epithelium in explant culture is dependent upon extracellular proline.
    J Cell Physiol. 1987 May;131(2):190-9 PMID: 3034921
  31. Reversible inhibition of mammary gland growth by transforming growth factor-beta.
    Science. 1987 Jul 17;237(4812):291-3 PMID: 3474783
  32. Local effects of EGF, alpha-TGF, and EGF-like growth factors on lobuloalveolar development of the mouse mammary gland in vivo.
    J Cell Physiol. 1987 Sep;132(3):581-4 PMID: 3498730
  33. Identification of a polypeptide growth inhibitor from bovine mammary gland. Sequence homology to fatty acid- and retinoid-binding proteins.
    J Biol Chem. 1987 Nov 5;262(31):15137-43 PMID: 3667628
  34. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Methods Enzymol. 1987;154:367-82 PMID: 3323813
  35. A 13-kilodalton protein purified from milk fat globule membranes is closely related to a mammary-derived growth inhibitor.
    Biochemistry. 1988 Mar 8;27(5):1420-5 PMID: 3365397
  36. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor.
    Dev Biol. 1988 Jun;127(2):304-15 PMID: 3259938
  37. Cloning of a full-length complementary DNA for fatty-acid-binding protein from bovine heart.
    Eur J Biochem. 1988 Aug 15;175(3):549-56 PMID: 3409882
  38. A mammary-derived growth inhibitor (MDGI) related 70 kDa antigen identified in nuclei of mammary epithelial cells.
    J Cell Physiol. 1989 Feb;138(2):415-23 PMID: 2918043
  39. A polypeptide growth inhibitor isolated from lactating bovine mammary gland (MDGI) is a lipid-carrying protein.
    J Cell Biochem. 1988 Nov;38(3):199-204 PMID: 3230093
  40. Specific high affinity binding of lipoxygenase metabolites of arachidonic acid by liver fatty acid binding protein.
    Biochem Biophys Res Commun. 1989 Jun 15;161(2):448-55 PMID: 2500117
  41. A 14-kilodalton selenium-binding protein in mouse liver is fatty acid-binding protein.
    J Biol Chem. 1989 Aug 15;264(23):13780-4 PMID: 2760043
  42. Fatty-acid-binding protein from bovine brain. Amino acid sequence and some properties.
    Eur J Biochem. 1989 Oct 20;185(1):35-40 PMID: 2806261
  43. Expression of extracellular matrix components is regulated by substratum.
    J Cell Biol. 1990 Apr;110(4):1405-15 PMID: 2182652
  44. Developmental regulation of mammary-derived growth inhibitor expression in bovine mammary tissue.
    J Cell Biol. 1990 May;110(5):1779-89 PMID: 2335570
  45. Mammary epithelial cells, extracellular matrix, and gene expression.
    Cancer Treat Res. 1991;53:365-81 PMID: 1672087
  46. Intracellular sterol distribution in transfected mouse L-cell fibroblasts expressing rat liver fatty acid-binding protein.
    J Biol Chem. 1991 Mar 25;266(9):5486-96 PMID: 2005092
  47. Designer microenvironments for the analysis of cell and tissue function.
    Curr Opin Cell Biol. 1990 Oct;2(5):864-74 PMID: 2083086
  48. Transforming growth factor-beta inhibits lactogenic hormone induction of beta-casein expression in HC11 mouse mammary epithelial cells.
    Growth Factors. 1990;4(1):9-15 PMID: 2085442
  49. New aspects of stroma-parenchyma relations in mammary gland differentiation.
    Int Rev Cytol. 1991;125:165-202 PMID: 2032784
  50. Modulation of the beta-adrenergic-response in cultured rat heart cells. II. Mammary-derived growth inhibitor (MDGI) blocks induction of beta-adrenergic supersensitivity. Dissociation from lipid-binding activity of MDGI.
    Mol Cell Biochem. 1991 Mar 27;102(1):49-60 PMID: 1646956
  51. Control of growth and differentiation of the mammary gland by growth factors.
    J Dairy Sci. 1991 Aug;74(8):2788-800 PMID: 1918550
  52. Isolation and sequence determination of cDNA encoding P2 protein of human peripheral myelin.
    Biochem Biophys Res Commun. 1991 Nov 27;181(1):204-7 PMID: 1720307
  53. Specific growth stimulation by linoleic acid in hepatoma cell lines transfected with the target protein of a liver carcinogen.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4830-4 PMID: 1594582
  54. Use of transgenic mice to map cis-acting elements in the intestinal fatty acid binding protein gene (Fabpi) that control its cell lineage-specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium.
    J Cell Biol. 1992 Oct;119(1):27-44 PMID: 1527171
  55. All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs.
    Cell. 1992 Oct 2;71(1):73-85 PMID: 1327537
  56. Hormonal induction of functional differentiation and mammary-derived growth inhibitor expression in cultured mouse mammary gland explants.
    In Vitro Cell Dev Biol. 1992 Sep-Oct;28A(9-10):625-34 PMID: 1429365
  57. Purification of a mammary-derived growth inhibitor (MDGI) related polypeptide expressed during pregnancy.
    Biochem Biophys Res Commun. 1992 Nov 30;189(1):406-13 PMID: 1280424
  58. TGF beta suppresses casein synthesis in mouse mammary explants and may play a role in controlling milk levels during pregnancy.
    J Cell Biol. 1993 Jan;120(1):245-51 PMID: 8416990
  59. Cytoplasmic fatty acid binding protein: significance for intracellular transport of fatty acids and putative role on signal transduction pathways.
    Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):33-41 PMID: 8424121
  60. Role of polyunsaturated fatty acids as signal transducers: amplification of signals from growth factor receptors by fatty acids in mammary epithelial cells.
    Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):71-8 PMID: 8424125
  61. Effects of epidermal growth factor, estrogen, and progestin on DNA synthesis in mammary cells in vivo are determined by the developmental state of the gland.
    J Cell Physiol. 1993 Apr;155(1):72-8 PMID: 8468371
  62. Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation.
    EMBO J. 1993 May;12(5):1835-45 PMID: 8491177
  63. The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium.
    Epithelial Cell Biol. 1993 Apr;2(2):79-89 PMID: 8353596
  64. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1.
    Genes Dev. 1993 Dec;7(12A):2308-17 PMID: 8253379
  65. Purification and characterisation of a polymorphic low M(r) bovine muscle cysteine proteinase inhibitor: structural identity with fatty-acid-binding proteins.
    Biochimie. 1993;75(10):937-45 PMID: 8312397
  66. Structural and functional aspects of cytosolic fatty acid-binding proteins.
    Prostaglandins Leukot Essent Fatty Acids. 1993 Dec;49(6):887-906 PMID: 8140117
  67. Endocrine control of mammarygland development and function in the C3H/ He Crgl mouse.
    J Natl Cancer Inst. 1958 Dec;21(6):1039-63 PMID: 13611531
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.127.4.1097
Published
1994-11-00
Pages
1097-109
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2200063
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.127.4.1097 PMC Full Text View journal details
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