Insulin and prolactin synergize to induce translation of human serum albumin in the mammary gland of transgenic mice
Tóm tắt
A dramatic uncoupling of the expression of chimaeric β-lactoglobulin (BLG)/human serum albumin (HSA) gene constructs at the RNA and protein levels was observed in cultured mammary explants of virgin transgenic mice. Upon explantation, both HSA RNA and protein were expressed at high levels. However, when the explants were grown in hormone-free medium, HSA RNA continued to accumulate, whereas the synthesis of the corresponding protein was dependent on the presence of insulin and prolactin with a minor contribution of hydrocortisone. The untranslated HSA RNA was indistinguishable from its translatable counterpart in its mobility on agarose gels, was transported normally from the nucleus to the cytoplasm and was translated efficiently in rabbit reticulocyte lysate. In the presence of cycloheximide, HSA RNA rapidly disappeared, suggesting a dependency on ongoing protein synthesis. Its estimated half-life of 5--6 h in hormone-free medium increased significantly in the presence o f insulin, hydrocortisone and prolactin and was comparable to that of β-casein RNA. The uncoupling of the expression of the BLG/HSA transgenes at the RNA and protein levels was also confirmed by in situ hybridization and immunohystochemistry on sections from virgin mammary explants. HSA synthesis was initiated within 13 h of the addition of insulin and prolactin in explants that had accumulated untranslated HSA RNA and was fourfold higher than that observed with insulin alone. Addition of hydrocortisone contributed to an additional 20% in HSA synthesis. We believe this is the first demonstration of translational control of exogenous milk protein gene expression in the mammary gland of transgenic animals
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Altiok, S. and Groner, B. (1994) β-casein mRNA sequesters a signal-stranded nucleic acid-binding protein which negatively regulates the β-casein gene promoter. Mol. Cell. Biol. 14, 6004-12.
Auffray, C. and Rougeon, F. (1980) Purification of mouse immunoglobulin heavy chain messenger RNAs from total myeloma tumor RNA. Eur. J. Biochem. 107, 303-14.
Barash, I., Faerman, A., Baruch, A., Nathan, M., Hurwitz, D.R. and Shani, M. (1993a) Synthesis and secretion of human serum albumin by mammary gland explants of virgin and lactating transgenic mice. Transgenic Res. 2, 266-76.
Barash, I., Baruch, A., Nathan, M., Shani, M. and Hurwitz, D.R. (1993b): HSA production by mammary explants of virgin transgenic mice. A reliable tool for predicting levels of secretion into milk. Animal Biotech. 4, 203-15.
Barash, I., Faerman, A., Ratovitsky, T., Puzis, R., Nathan, M., Hurwitz, D.R. and Shani, M. (1994) Ectopic expression of β-lactoglobulin/human serum albumin fusion genes in transgenic mice: hormonal regulation and in situ localization. Transgenic Res. 3, 141-51.
Barash, I., Faerman, A., Puzis, R., Peterson, D. and Shani, M. (1995) Synthesis and secretion of caseins by the mouse mammary gland: production and characterization of new polyclonal antibodies. Mol. Cell. Biochem. 144, 175-80.
Baruch, A., Shani, M., Hurwitz, D.R. and Barash, I. (1995) Developmental regulation of the ovine β-lactoglobulin/human serum albumin transgene is distinct from that of the β-lactoglobulin and the endogenous β-casein genes in the mammary gland of transgenic mice. Dev. Genetics 16, 241-52.
Bchini, O., Andres, A.C., Schubaur, B., Mehtali, M., LeMeur, M., Lathe, R. and Gerlinger, P. (1991) Precocious mammary gland development and milk protein synthesis in transgenic mice ubiquitously expressing human growth hormone. Endocrinology 128, 539-46.
Bolander, F.F. Jr., Nicholas, K.R., Van Wyk, J.J. and Topper, Y.J. (1981) Insulin is essential for accumulation of casein mRNA in mouse mammary epithelial cells. Proc. Natl Acad. Sci. USA 78, 5682-84.
Buckley, A.R., Rao, Y.-P., Buckley, D.J., Gout, P.W. (1994) Prolactin-induced phosphorylation and nuclear translocation of MAP kinase in Nb2 lymphoma cells. Biochem. Biophys. Res. Comm. 204, 1158-64.
Campbell, G.S., Argetsinger, L.S., Ihle, J.N., Kelly, P.A., Rillema, J.A, Carter-Su, C. (1994) Activation of JAK2 tyrosine kinase by prolactin receptors in Nb2 cells and mouse mammary gland explants. Proc. Natl Acad. Sci. USA 91, 5232-36.
Camps, M., Vilaro, S., Testar, X., Palacin, M. and Zorzano, A. (1994) High and polarized expression of GLUT1 glucose transporter in epithelial cells from mammary gland: acute down-regulation of GLUT1 carries by weaning. Endocrinology 134, 924-34.
Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chlorophorm extraction. Anal. Biochem. 162, 156-9.
Chomczynski, P., Qasba, P. and Topper, Y.J. (1984) Essential role of insulin in transcription of the rat 25,000 molecular weight casein gene. Science 226, 1326-8.
Chomczynski, P., Qasba, P., Topper, Y.J (1986) Transcriptional and post-transcriptional roles of glucocorticoids in the expression of the rat 25,000 molecular weight casein gene. Biochem. Biophys. Res. Commun. 134, 812-8.
Curtis, D., Lehmann, R. and Zamore, P.D. (1995) Translational regulation of development. Cell 81, 171-8.
Das, R. and Vonderhaar, B.K. (1995) Transduction of prolactin's (PRL) growth signal through both long and short forms of the PRL receptor. Mol. Endocrinol. 9, 1750-9.
Dusanter-Fourt, I., Muller, O., Ziemiecki, A., Mayeux, P., Drucker, B., Djiane, J., Wilks, A., Harpur, A.G., Fischer, S. and Gisselbrecht, S. (1994) Identification of JAK protein tyrosine kinase as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. EMBO J. 13, 2583-91.
Eisenstein, R.S. and Rosen, J.M. (1988) Both cell-substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the post-transcription level. Mol. Cell. Biol. 8, 3183-90.
Faerman, A., Barash, I., Puzis, R., Nathan, M., Hurwitz, D.R. and Shani, M. (1995) Dramatic heterogeneity of transgene expression in the mammary gland of lactating mice: a model system to study the synthetic activity of mammary epithelial cells. J. Hystochem. Cytochem. 43, 461-70.
Faulkner, A. and Peaker, M. (1987) Regulation of mammary glucose metabolism in lactation. In Neville M.C. and Daniel, C.W. eds., The Mammary Gland. pp. 535-62. New York, USA; Plenum Press.
Gouilleux, F., Wakao, H., Mundt, M. and Groner, B. (1994) Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 13, 4361-9.
Gray, N.K. and Hentze, M.W. (1994) Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. EMBO J. 13, 3882-91.
Guyette, W.A., Matusik, R.J. and Rosen, J.M. (1979) Prolactin mediated transcriptional and post-transcriptional control of casein gene expression. Cell 17, 1013-23.
Hentze, M.W. (1995) Translational regulation: versatile mechanisms for metabolic and developmental control. Current Opinion Cell Biol. 7, 393-8.
Hobbs, A.A., Richards, D.A., Kessler, D.J. and Rosen, J.M. (1982) Complex hormonal regulation of rat casein gene expression. J. Biol. Chem. 257, 3598-605.
Houdebine, L.M., Djiane, J., Dusanter-Fourt, I., Martel, P., Kelly, P., Devinoy, E. and Servely, J.L. (1985) Hormonal action controlling mammary activity. J. Dairy Sci. 68, 489-500.
Hurwitz, D.R., Nathan, M., Barash, I., Ilan, N. and Shani, M. (1994) Specific combinations of human serum albumin introns direct high level expression of albumin in transfected COS cells and in the milk of transgenic mice. Transgenic Res. 3, 365-75.
Ilan, N., Barash, I., Faerman, A. and Shani, M. (1996) Dual regulation of β-lactoglobulin/human serum albumin gene expression by the extracellular matrix in mammary cells from transgenic mice. Exp. Cell Res. 224, 28-38.
Ivashkiv, L.B. (1995) Cytokines and STATs: how can signals achieve specificity? Immunity 3, 1-4.
Kazansky, A.V., Raught, B., Lindsey, S.M., Wang, Y.F. and Rosen, J.M. (1995) Regulation of mammary gland factor/Stat5a during mammary gland development. Mol. Endocrinol. 9, 1598-609.
Kelly, P.A., Djiane, J., Postel-Vinay, M.C. and Edrey, M. (1991) The prolactin/growth hormone receptor family. Endocrine Rev. 12, 235-51.
Kishimoto, T., Taga, T. and Akira, S. (1994) Cytokine signal transduction. Cell 76, 253-62.
Kolb, A.F., Gunzburg, W.H., Albang, R., Brem, G., Erfle, V. and Salmons, B. (1994) Negative regulatory element in the mammary specific whey acidic protein promoter. J. Cell Biochem. 56, 245-61.
Kozak, M. (1991a) Structural features in eukaryotic mRNAs that modulate the initiation of translation. J. Biol. Chem. 266, 19867-70.
Kozak, M. (1991b) An analysis of vertebrate mRNA sequences: Intimations of translational control. J. Cell. Biol. 115, 887-903.
Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-5.
Lebrun, J.J., Ali, S., Sofer, L., Ullrich, A. and Kelly, P.A. (1994) Prolactin-induced proliferation of Nb2 cells involves tyrosine phosphorylation of the prolactin receptor and its associated tyrosine kinase JAK2. J. Biol. Chem. 269, 14021-6.
Lee, E.Y.H.P., Lee, W-H., Kaetzel, C.H., Parry, G. and Bissell, M.J. (1985) Interaction of mouse mammary epithelial cells with collagen substrata: Regulation of casein gene expression and secretion. Proc. Natl Acad. Sci. USA 82, 1419-23.
Li, S. and Rosen, J.M. (1994) Glucocorticoid regulation of rat whey acidic protein gene expression involves hormone-induced alterations of chromatin structure in the distal promoter region. Mol. Endocrinol. 8, 1328-35.
Li, S. and Rosen, J.M. (1995) Nuclear factor I and mammary gland factor (STAT5) play a critical role in regulating rat whey acidic protein gene expression in transgenic mice. Mol. Cell. Biol. 15, 2063-70.
Lin, T.A., Kong, X., Haystead, T.A.J., Pause, A., Belsham, G., Sonenberg, N. and Lawrence, J.C., Jr (1994) PHSA-I as a link between mitogen-activated protein kinase and translation initiation. Science 266, 653-56.
Lin, T.A., Kong, X., Saltiel, A.R., Blackshear, P.J. and Lawrence, J.C., Jr. (1995) Control of PHSA-I by insulin in 3T3-L1 adipocytes. J. Biol. Chem. 270, 18531-8.
McCarthy, J.E.G. and Kollmus, H. (1995) Cytoplasmatic mRNA-protein interactions in eukaryotic gene expression. Trends Biochem. 20, 191-7.
Nevins, J.R. (1983) The pathway of eukaryotic mRNA formation. Ann. Rev. Biochem. 52, 441-66.
O'Brien, R.M. and Granner, D.K. (1991) Regulation of gene expression by insulin. Biochem. J. 278, 609-19.
Pause, A., Belsham, G.J., Gingras, A-C., Donze, O., Lin T-A., Lawrence, J.C. Jr. and Sonenberg, N. (1994) Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371, 762-7.
Piccoletti, R., Maroni, P., Bendinelli, P. and Bernelli-Zazzera, A. (1994) Rapid stimulation of mitogen-activated protein kinase of rat liver by prolactin. Biochem. J. 303, 429-33.
Pittius, C.W., Sankaran, L., Topper, Y.J. and Hennighausen, L. (1988) Comparison of the regulation of the whey acidic protein gene to a hybrid gene containing the whey acidic protein gene promoter in transgenic mice. Mol. Endocrinol. 3, 1027-32.
Poyet, P., Henning, S.J. and Rosen, J.M. (1989) Hormone-dependent β-casein mRNA stabilization requires ongoing protein synthesis. Mol. Endocrinol. 3, 1961-8.
Proud, C.G. (1994) Turned on by insulin. Nature 371, 747-8.
Razooki Hasan, H., White, D.A. and Mayer, R.J. (1982) Extensive destruction of newly synthesized casein in mammary explants in organ culture. Biochem. J. 202, 133-8.
Roy, S.K. and Greenwald, G.S. (1986) Quantitative analysis of invitro incorporation of [3H]thymidine into hamster follicles during oestrous cycle. J. Reprod. Fert. 77, 143-52.
Rui, H., Kirken, R.A. and Farrar, W.L. (1994) Activation of receptor-associated tyrosine kinase JAK2 by prolactin. J. Biol. Chem. 269, 5364-8.
Rousseau, D., Kaspar, R., Rosenwald, I., Gehrke, L. and Sonenberg, N. (1996) Translation initiation of ornithine decrboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc. Natl Acad. Sci. USA 93, 1065-70.
Schibler, U. and Wuarin, J. (1990) Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell 63, 1257-66.
Schmitt-Ney, M., Happ, B., Hofer, P., Hynes, N.E. and Groner, B. (1992) Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis. Mol. Endocrinol. 6, 1988-97.
Shani, M., Barash, I., Nathan, M., Ricca, G., Searfoss, G.H., Dekel, I., Faerman, A., Givol, D. and Hurwitz, D.R. (1992) Expression of human serum albumin in the milk of transgenic mice. Transgenic Res. 1, 195-208.
Snedecor, G.W. and Cochran, W.G. (1967) Statistical Methods, 6th Edn. Ames, Iowa, USA: Iowa State University Press.
Standart, N. and Jackson, R. (1994) Y the massage is masked? Curr. Biol. 4, 939-41.
Streuli, C.H., Edwards, G.M., Delcommenne, M., Whitelaw, C.B.A., Burdon, T.G., Schindler, C. and Watson, C.J. (1995) Stat5 as a target for regulation by extracellular matrix. J. Biol. Chem. 270, 21639-44.
Topper, Y.J. and Freeman, C.S. (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol. Rev. 60, 1049-106.
Topper, Y.J., Oka, T. and Vonderhaar, B.K. (1975) Techniques for studying development of normal epithelial cells in organ culture. Meth. Enzymol. 39, 443-54.
Tourkine, N., Schindler, C., Larose, M. and Houdebine, L.M. (1995) Activation of STAT factors by prolactin, interferon-γ, growth hormones, and a tyrosine phosphataes inhibitor in rabbit primary mammary epithelial cells. J. Biol. Chem. 270, 20952-61.
Vonderhaar, B.K. (1987) Prolactin: transport, function, and receptors in mammary gland development and differentiation. In: Neville, M.C., Daniel, C.W. eds., The Mammary Gland. pp. 383-417 New York, USA: Plenum Press.
Vonderhaar, B.K. and Ziska, S.E. (1989) Hormonal regulation of milk protein gene expression. Annu. Rev. Physiol. 51, 641-52.
Wakao, H., Gouilleux, F. and Groner, B. (1994) Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 13, 2182-91.
Welte, T., Garimorth, K., Philipp, S. and Doppler, W. (1994) Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in mouse mammary epithelial cells. Mol. Endocrinol. 8, 1091-102.
Yoshimura, M. and Oka, T. (1989) Isolation and structural analysis of the mouse β-casein gene. Gene 78, 267-75.
Yoshimura, M. and Oka, T. (1990) Hormonal induction of β-casein gene expression: requirement of ongoing protein synthesis for transcription. Endocrinology 126, 427-33.