c-Myc affects mRNA translation, cell proliferation and progenitor cell function in the mammary gland

Autor: Nancy E. Hynes, Tina Stoelzle, Patrick Schwarb, Andreas Trumpp
Rok vydání: 2009
Předmět:
Physiology
Cellular differentiation
Mammary gland
Cell Count
Plant Science
Biology
General Biochemistry
Genetics and Molecular Biology
Proto-Oncogene Proteins c-myc
Mice
Mammary Glands
Animal
Pregnancy
Structural Biology
Conditional gene knockout
medicine
Animals
Lactation
RNA
Messenger
Progenitor cell
lcsh:QH301-705.5
Ecology
Evolution
Behavior and Systematics
Cell Proliferation
Mammary tumor
Agricultural and Biological Sciences(all)
Integrases
Biochemistry
Genetics and Molecular Biology(all)
Cell growth
Stem Cells
Gene targeting
Cell Differentiation
Cell Biology
Molecular biology
Cell biology
Milk
medicine.anatomical_structure
lcsh:Biology (General)
Protein Biosynthesis
Gene Targeting
Female
Stem cell
General Agricultural and Biological Sciences
Ribosomes
Gene Deletion
Research Article
Developmental Biology
Biotechnology
Zdroj: BMC Biology
BMC Biology, Vol 7, Iss 1, p 63 (2009)
ISSN: 1741-7007
Popis: Background The oncoprotein c-Myc has been intensely studied in breast cancer and mouse mammary tumor models, but relatively little is known about the normal physiological role of c-Myc in the mammary gland. Here we investigated functions of c-Myc during mouse mammary gland development using a conditional knockout approach. Results Generation of c-myc fl/fl mice carrying the mammary gland-specific WAPiCre transgene resulted in c-Myc loss in alveolar epithelial cells starting in mid-pregnancy. Three major phenotypes were observed in glands of mutant mice. First, c-Myc-deficient alveolar cells had a slower proliferative response at the start of pregnancy, causing a delay but not a block of alveolar development. Second, while milk composition was comparable between wild type and mutant animals, milk production was reduced in mutant glands, leading to slower pup weight-gain. Electron microscopy and polysome fractionation revealed a general decrease in translational efficiency. Furthermore, analysis of mRNA distribution along the polysome gradient demonstrated that this effect was specific for mRNAs whose protein products are involved in milk synthesis. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed decreased levels of ribosomal RNAs and ribosomal protein-encoding mRNAs in mutant glands. Third, using the mammary transplantation technique to functionally identify alveolar progenitor cells, we observed that the mutant epithelium has a reduced ability to repopulate the gland when transplanted into NOD/SCID recipients. Conclusion We have demonstrated that c-Myc plays multiple roles in the mouse mammary gland during pregnancy and lactation. c-Myc loss delayed, but did not block proliferation and differentiation in pregnancy. During lactation, lower levels of ribosomal RNAs and proteins were present and translation was generally decreased in mutant glands. Finally, the transplantation studies suggest a role for c-Myc in progenitor cell proliferation and/or survival. See related minireview by Evan et al: http://jbiol.com/content/8/8/77
Databáze: OpenAIRE
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