Is the Mannose-6-Phosphate/Insulin-Like Growth Factor 2 Receptor Coded by a Breast Cancer Suppressor Gene?

  • Guy Joseph Lemamy
  • Majida Esslimani Sahla
  • Marie Laurence Berthe
  • Pascal Roger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)


The multifunctional growth factor mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2-R) binds proteins sharing M6P signals, including cathepsins and IGF2. It is involved in targeting newly synthesized mannose-6-phosphorylated lysosomal enzymes, activating transforming growth factor β (TGFβ), and neutralising the mitogen IGF2 by transporting it to lysosomes. The M6P/IGF2-R was proposed as being coded by a tumor suppressor gene. We measured gene expression at the protein level by quantitative immunohistochemistry, using chicken high affinity IgY antibodies directed against human M6P/IGF2-R. Chicken immunization was performed with human purified M6P/IGF2-R, and IgY antibodies were extracted from egg yolk by polyethylene glycol precipitation method. The biosensor analysis showed that IgY antibodies bind M6P/IGF2-R with high affinity (Kd = 7.5 nM). Quantitative immunohistochemical studies in sections from invasive breast carcinoma and ductal carcinoma in situ (DCIS) indicated various levels (from 5 to 400 units) of the M6P/IGF2-R protein, which did not correlate with tumor size, histological grade, estrogen and progesterone receptors. Moreover, the M6P/IGF2-R level was increased in DCIS relative to adjacent normal tissue (p < 0.005) and then decreased in invasive carcinoma compared with DCIS (p < 0.02). The hypothesis of tumor suppressor gene is not supported by these studies. However, it is not excluded for a small proportion of the tumors. Its assay might help to complement the cathepsin D assay to predict breast cancer prognosis and physiopathology.


Invasive Breast Cancer Adjacent Normal Tissue Benign Breast Disease Invasive Breast Carcinoma Normal Lobule 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Guy Joseph Lemamy
    • 1
  • Majida Esslimani Sahla
    • 2
  • Marie Laurence Berthe
  • Pascal Roger
    • 3
  1. 1.Faculte de MedecineUniversite des Sciences de la SanteLibreville (Central Africa)Gabon
  2. 2.Department of PathologieCRLC Val D’Aurelle ParcEuromedecineMontpellierFrance
  3. 3.Lab. D’Anatomie et Cytologie PatholHospital LapeyronieMontpellierFrance

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