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Reducing mammary cancer risk through premature stem cell senescence

Oncogene volume 20, pages 2264–2272 (2001)Cite this article

Abstract

The reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. In a study of FVB/N mice with the transgene, WAP-TGFβ1, we discovered that mammary epithelial stem cells were prematurely aged due to ectopic expression of TGF-β1. To test whether premature aging of mammary epithelial stem cells would have an impact on susceptibility or resistance to mammary cancer, female littermates from FVB/N×WAP-TGF-β1 mating were injected with mouse mammary tumor virus (MMTV) at 8–10 weeks of age. A total of 44 females were inoculated, maintained as breeders and observed for tumor development for up to 18 months. Only one mammary tumor appeared in 17 TGF-β1 females while 15 were collected from 29 wild type sisters. Premalignant mammary epithelial cells in infected glands were identified by transplantation of single cell (1×105) suspensions into nulliparous hosts and testing for hyperplastic outgrowth. Although the number of positive takes was significantly reduced with TGF-β1 cells, both MMTV-infected TGF-β1 and wild type cells produced hyperplastic outgrowths suggesting that premalignant transformation was achieved in each group. The results suggest a positive correlation between the procreative life-span of mammary epithelial stem cells and mammary cancer risk.

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References

  • Arthur LO, Long CW, Smith GH, Fine DL . 1978 Int. J. Cancer 22: 433–440

  • Buggiano V, Schere-Levy C, Abe K, Vanzulli S, Piazzon I, Smith GH, Kordon EC . 2001 Int. J. Cancer In the press

  • Daniel CW, De Ome KB, Young JT, Blair PB, Faulkin Jr LJ . 1968 Proc. Natl. Acad. Sci. USA 61: 53–60

  • Daniel CW, Young LJ . 1971 Exp. Cell. Res. 65: 27–32

  • Daniel CW, Young LJ, Medina D, DeOme KB . 1971 Exp. Gerontol. 6: 95–101

  • DeOme KB, Faulkin LJ, Bern HA, Blair PB . 1959 Cancer Res. 78: 515–520

  • DeOme KB, Miyamoto MJ, Osborn RC, Guzman RC, Lum K . 1978a Cancer Res. 38: 2103–2111

  • DeOme KB, Miyamoto MJ, Osborn RC, Guzman RC, Lum K . 1978b Cancer Res. 38: 4050–4053

  • Felluga B, Claude A, Mrena E . 1969 J. Natl. Cancer Inst. 43: 319–333

  • Heine U, Munoz EF, Flanders KC, Ellingsworth LR, Lam HY, Thompson NL, Roberts AB, Sporn MB . 1987 J. Cell. Biol. 105: 2861–2876

  • Held W, Acha-Orbea H, MacDonald HR, Waanders GA . 1994 Immunol. Today 15: 184–190

  • Hook LM, Agafonova Y, Ross SR, Turner SJ, Golovkina TV . 2000 J. Virol. 74: 8876–8883

  • Imai S, Okumoto M, Iwai M, Haga S, Mori N, Miyashita N, Moriwaki K, Hilgers J, Sarkar NH . 1994 J. Virol. 68: 3437–3442

  • Jhappan C, Geiser AG, Kordon EC, Bagheri D, Hennighausen L, Roberts AB, Smith GH, Merlino G . 1993 EMBO J. 12: 1835–1845

  • Kamiya K, Higgins PD, Tanner MA, Gould MN, Clifton KH . 1999 J. Radiat. Res. (Tokyo) 40: Suppl 128–137

  • Katakura Y, Nakata E, Miura T, Shirahata S . 1999 Biochem. Biophys. Res. Commun. 255: 110–115

  • Kingsley DM . 1994 Genes Dev. 8: 133–146

  • Kordon EC, McKnight RA, Jhappan C, Hennighausen L, Merlino G, Smith GH . 1995 Dev. Biol. 168: 47–61

  • Kordon EC, Smith GH . 1998 Development 125: 1921–1930

  • Massague J . 1990 Annu. Rev. Cell. Biol. 6: 597–641

  • Medina D . 1973 Methods Cancer Res. 7: 3–53

  • Nicoll CS, Tucker HA . 1965 Life Sci. 4: 993–1001

  • Pierce Jr DF, Gorska AE, Chytil A, Meise KS, Page DL, Coffey Jr RJ, Moses HL . 1995 Proc. Natl. Acad. Sci. USA 92: 4254–4258

  • Rasmussen SB, Young LJT, Smith GH . 2000 Methods in Mammary Gland Biology and Cancer Research. Ip MaAB (ed.) Plenum: New York pp. 75–85

  • Ross SR . 1998 Immunol. Res. 17: 209–216

  • Roubinian JR, Blair PB . 1980 J. Natl. Cancer Inst. 65: 795–800

  • Sell S, Pierce GB . 1994 Lab. Invest. 70: 6–22

  • Smith GH . 1996 Breast Cancer Res. Treat. 39: 21–31

  • Smith GH, Vonderhaar BK, Graham DE, Medina D . 1984 Cancer Res. 44: 3426–3437

  • Southern EM . 1975 J. Mol. Biol. 98: 503–517

  • Sporn MB, Roberts AB . 1992 J. Cell Biol. 119: 1017–1021

  • Squartini F, Basolo F, Bistocchi M . 1983 Cancer Res. 43: 5879–5882

  • Van Nie R, Verstraeten AA, De Moes J . 1977 Int. J. Cancer 19: 383–390

  • Yang HAS, L . 2000 Proc. Am. Assoc. Cancer Res. 41: 225

  • Young LJ, Medina D, DeOme KB, Daniel CW . 1971 Exp. Gerontol. 6: 49–56

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  1. Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, 20892, Maryland, MD, USA

    Corinne A Boulanger & Gilbert H Smith

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  1. Corinne A Boulanger
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  2. Gilbert H Smith
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Boulanger, C., Smith, G. Reducing mammary cancer risk through premature stem cell senescence. Oncogene 20, 2264–2272 (2001). https://doi.org/10.1038/sj.onc.1204312

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