title: Is the mannose-6-phosphate/insulin-like growth factor 2 receptor coded by a breast cancer suppressor gene?
abstract: 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 beta (TGFbeta), 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.
authors.affiliation: Faculte de Medecine, Universite des Sciences de la Sante, Libreville (Central Africa), Gabon.
authors.forename: Guy Joseph
authors.initials: GJ
authors.lastname: Lemamy
authors.forename: Majida Esslimani
authors.initials: ME
authors.lastname: Sahla
authors.forename: Marie Laurence
authors.initials: ML
authors.lastname: Berthe
authors.forename: Pascal
authors.initials: P
authors.lastname: Roger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008360:Mannosephosphates / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011446:Prospective Studies; D017527:Receptor, IGF Type 2 / Q000235:genetics*
chemical_list: D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate