Deregulated expression of c-Myc depletes epidermal stem cells - PubMed (original) (raw)

Deregulated expression of c-Myc depletes epidermal stem cells

R L Waikel et al. Nat Genet. 2001 Jun.

Abstract

The beta-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of beta-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2). Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding. The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice. Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice. We conclude that deregulated expression of c-Myc in stem cells reduces beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance.

PubMed Disclaimer

Similar articles

• Targeted expression of c-Myc in the epidermis alters normal proliferation, differentiation and UV-B induced apoptosis.
  Waikel RL, Wang XJ, Roop DR. Waikel RL, et al. Oncogene. 1999 Aug 26;18(34):4870-8. doi: 10.1038/sj.onc.1203040. Oncogene. 1999. PMID: 10490820
• In vitro characteristics of early epidermal progenitors isolated from keratin 14 (K14)-deficient mice: insights into the role of keratin 17 in mouse keratinocytes.
  Troy TC, Turksen K. Troy TC, et al. J Cell Physiol. 1999 Sep;180(3):409-21. doi: 10.1002/(SICI)1097-4652(199909)180:3<409::AID-JCP12>3.0.CO;2-V. J Cell Physiol. 1999. PMID: 10430181
• Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis.
  Braun KM, Niemann C, Jensen UB, Sundberg JP, Silva-Vargas V, Watt FM. Braun KM, et al. Development. 2003 Nov;130(21):5241-55. doi: 10.1242/dev.00703. Epub 2003 Sep 3. Development. 2003. PMID: 12954714
• Epidermal stem cells: markers, patterning and the control of stem cell fate.
  Watt FM. Watt FM. Philos Trans R Soc Lond B Biol Sci. 1998 Jun 29;353(1370):831-7. doi: 10.1098/rstb.1998.0247. Philos Trans R Soc Lond B Biol Sci. 1998. PMID: 9684280 Free PMC article. Review.
• Epithelial stem cells.
  Jones PH. Jones PH. Bioessays. 1997 Aug;19(8):683-90. doi: 10.1002/bies.950190808. Bioessays. 1997. PMID: 9264250 Review.

Cited by

• MYC suppresses cancer metastasis by direct transcriptional silencing of αv and β3 integrin subunits.
  Liu H, Radisky DC, Yang D, Xu R, Radisky ES, Bissell MJ, Bishop JM. Liu H, et al. Nat Cell Biol. 2012 May 13;14(6):567-74. doi: 10.1038/ncb2491. Nat Cell Biol. 2012. PMID: 22581054 Free PMC article.
• Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1.
  Wells J, Lee B, Cai AQ, Karapetyan A, Lee WJ, Rugg E, Sinha S, Nie Q, Dai X. Wells J, et al. J Biol Chem. 2009 Oct 16;284(42):29125-35. doi: 10.1074/jbc.M109.008847. Epub 2009 Aug 21. J Biol Chem. 2009. PMID: 19700410 Free PMC article.
• Label retaining cells and cutaneous stem cells.
  Terskikh VV, Vasiliev AV, Vorotelyak EA. Terskikh VV, et al. Stem Cell Rev Rep. 2012 Jun;8(2):414-25. doi: 10.1007/s12015-011-9299-6. Stem Cell Rev Rep. 2012. PMID: 21744048 Review.
• Analysis of the human pancreatic stellate cell secreted proteome.
  Wehr AY, Furth EE, Sangar V, Blair IA, Yu KH. Wehr AY, et al. Pancreas. 2011 May;40(4):557-66. doi: 10.1097/MPA.0b013e318214efaf. Pancreas. 2011. PMID: 21499210 Free PMC article.
• piggyBac transposon somatic mutagenesis with an activated reporter and tracker (PB-SMART) for genetic screens in mice.
  Landrette SF, Cornett JC, Ni TK, Bosenberg MW, Xu T. Landrette SF, et al. PLoS One. 2011;6(10):e26650. doi: 10.1371/journal.pone.0026650. Epub 2011 Oct 21. PLoS One. 2011. PMID: 22039523 Free PMC article.

Publication types

MeSH terms

Substances

Grants and funding

• AR62228/AR/NIAMS NIH HHS/United States
• CA09197/CA/NCI NIH HHS/United States
• CA52607/CA/NCI NIH HHS/United States
• CA79998/CA/NCI NIH HHS/United States
• HD25479/HD/NICHD NIH HHS/United States

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal