Is the mannose-6-phosphate/insulin-like growth factor 2 receptor coded by a breast cancer suppressor gene?
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.
Lemamy
Guy Joseph
GJ
Faculte de Medecine, Universite des Sciences de la Sante, Libreville (Central Africa), Gabon.
Sahla
Majida Esslimani
ME
Berthe
Marie Laurence
ML
Roger
Pascal
P
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*
D008360:Mannosephosphates; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate