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. 1998 Aug 15;334(Pt 1):205–210. doi: 10.1042/bj3340205

Expression of the genes encoding CCAAT-enhancer binding protein isoforms in the mouse mammary gland during lactation and involution.

G Sabatakos 1, G E Davies 1, M Grosse 1, A Cryer 1, D P Ramji 1
PMCID: PMC1219680  PMID: 9693121

Abstract

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the activation of gene expression in the mammary gland during lactation. We have therefore investigated the detailed expression profile of the C/EBP family during lactation and involution of the mouse mammary gland. The expression of C/EBPbeta and C/EBPdelta mRNA was low during lactation, increased dramatically at the beginning of involution and remained constant thereafter. In contrast, C/EBPalpha mRNA expression was relatively high during the early stages of lactation, declined to low levels during the late stages of lactation and at the start of involution, and increased again during involution. Electrophoretic mobility-shift assays showed a close correlation between the expression of the C/EBP genes and the functional C/EBP DNA-binding activity and, additionally, demonstrated the participation of heterodimers, formed from among the three proteins, in DNA-protein interactions. The DNA-binding activity of the activator protein 1 (AP1) family of transcription factors was also induced during involution. These results therefore point to potentially important regulatory roles for both the C/EBP and the AP1 family during lactation and involution of the mammary gland.

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Selected References

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  1. Buck M., Turler H., Chojkier M. LAP (NF-IL-6), a tissue-specific transcriptional activator, is an inhibitor of hepatoma cell proliferation. EMBO J. 1994 Feb 15;13(4):851–860. doi: 10.1002/j.1460-2075.1994.tb06328.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  3. Descombes P., Schibler U. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell. 1991 Nov 1;67(3):569–579. doi: 10.1016/0092-8674(91)90531-3. [DOI] [PubMed] [Google Scholar]
  4. Diehl A. M., Yang S. Q. Regenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to the C/EBP site in the c-fos promoter. Hepatology. 1994 Feb;19(2):447–456. [PubMed] [Google Scholar]
  5. Doppler W., Welte T., Philipp S. CCAAT/enhancer-binding protein isoforms beta and delta are expressed in mammary epithelial cells and bind to multiple sites in the beta-casein gene promoter. J Biol Chem. 1995 Jul 28;270(30):17962–17969. doi: 10.1074/jbc.270.30.17962. [DOI] [PubMed] [Google Scholar]
  6. Eckert R. L., Welter J. F. Epidermal keratinocytes - genes and their regulation. Cell Death Differ. 1996 Oct;3(4):373–383. [PubMed] [Google Scholar]
  7. Enerbäck S., Gimble J. M. Lipoprotein lipase gene expression: physiological regulators at the transcriptional and post-transcriptional level. Biochim Biophys Acta. 1993 Aug 11;1169(2):107–125. doi: 10.1016/0005-2760(93)90196-g. [DOI] [PubMed] [Google Scholar]
  8. Gigliotti A. P., DeWille J. W. Lactation status influences expression of CCAAT/enhancer binding protein isoform mRNA in the mouse mammary gland. J Cell Physiol. 1998 Feb;174(2):232–239. doi: 10.1002/(SICI)1097-4652(199802)174:2<232::AID-JCP10>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  9. Guenette R. S., Corbeil H. B., Léger J., Wong K., Mézl V., Mooibroek M., Tenniswood M. Induction of gene expression during involution of the lactating mammary gland of the rat. J Mol Endocrinol. 1994 Feb;12(1):47–60. doi: 10.1677/jme.0.0120047. [DOI] [PubMed] [Google Scholar]
  10. Jensen D. R., Gavigan S., Sawicki V., Witsell D. L., Eckel R. H., Neville M. C. Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse. Biochem J. 1994 Mar 1;298(Pt 2):321–327. doi: 10.1042/bj2980321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lund L. R., Rømer J., Thomasset N., Solberg H., Pyke C., Bissell M. J., Danø K., Werb Z. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways. Development. 1996 Jan;122(1):181–193. doi: 10.1242/dev.122.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MacDougald O. A., Lane M. D. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem. 1995;64:345–373. doi: 10.1146/annurev.bi.64.070195.002021. [DOI] [PubMed] [Google Scholar]
  13. Marti A., Jehn B., Costello E., Keon N., Ke G., Martin F., Jaggi R. Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells. Oncogene. 1994 Apr;9(4):1213–1223. [PubMed] [Google Scholar]
  14. Müller C., Kowenz-Leutz E., Grieser-Ade S., Graf T., Leutz A. NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line. EMBO J. 1995 Dec 15;14(24):6127–6135. doi: 10.1002/j.1460-2075.1995.tb00303.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. O'Rourke J., Yuan R., DeWille J. CCAAT/enhancer-binding protein-delta (C/EBP-delta) is induced in growth-arrested mouse mammary epithelial cells. J Biol Chem. 1997 Mar 7;272(10):6291–6296. doi: 10.1074/jbc.272.10.6291. [DOI] [PubMed] [Google Scholar]
  16. Ossipow V., Descombes P., Schibler U. CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8219–8223. doi: 10.1073/pnas.90.17.8219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Philp J. A., Burdon T. G., Watson C. J. Differential activation of STATs 3 and 5 during mammary gland development. FEBS Lett. 1996 Oct 28;396(1):77–80. doi: 10.1016/0014-5793(96)01069-1. [DOI] [PubMed] [Google Scholar]
  18. Poli V., Mancini F. P., Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990 Nov 2;63(3):643–653. doi: 10.1016/0092-8674(90)90459-r. [DOI] [PubMed] [Google Scholar]
  19. Ramji D. P., Tadros M. H., Hardon E. M., Cortese R. The transcription factor LF-A1 interacts with a bipartite recognition sequence in the promoter regions of several liver-specific genes. Nucleic Acids Res. 1991 Mar 11;19(5):1139–1146. doi: 10.1093/nar/19.5.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ramji D. P., Vitelli A., Tronche F., Cortese R., Ciliberto G. The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms. Nucleic Acids Res. 1993 Jan 25;21(2):289–294. doi: 10.1093/nar/21.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raught B., Liao W. S., Rosen J. M. Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression. Mol Endocrinol. 1995 Sep;9(9):1223–1232. doi: 10.1210/mend.9.9.7491114. [DOI] [PubMed] [Google Scholar]
  22. Strange R., Li F., Saurer S., Burkhardt A., Friis R. R. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development. 1992 May;115(1):49–58. doi: 10.1242/dev.115.1.49. [DOI] [PubMed] [Google Scholar]
  23. Talhouk R. S., Bissell M. J., Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992 Sep;118(5):1271–1282. doi: 10.1083/jcb.118.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wedel A., Ziegler-Heitbrock H. W. The C/EBP family of transcription factors. Immunobiology. 1995 Jul;193(2-4):171–185. doi: 10.1016/s0171-2985(11)80541-3. [DOI] [PubMed] [Google Scholar]
  25. Yeh W. C., Cao Z., Classon M., McKnight S. L. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995 Jan 15;9(2):168–181. doi: 10.1101/gad.9.2.168. [DOI] [PubMed] [Google Scholar]
  26. de Groot R. P., Sassone-Corsi P. Activation of Jun/AP-1 by protein kinase A. Oncogene. 1992 Nov;7(11):2281–2286. [PubMed] [Google Scholar]

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