Increased levels of mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2-R) found in serum of patients with breast cancer

Lemamy Guy Joseph, Ndeboko Benedicte, Omouessi Serge Thierry, Mouecoucou Justine
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Abstract

The multifunctional transmembrane mannose-6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2-R) has been proposed as a putative prognostic marker in breast cancer. Loss of heterozygosity (LOH) with mutations in the remaining allele have been described at the gene level. We previously reported significant decrease of M6P/IGF2-R at the protein level in cancer cells than normal peritumoral ducts of breast tumors which may indicate an increased release of the receptor from the cell membrane to the blood. To assess that hypothesis we measured in this study M6P/IGF2-R levels in serum of women with breast cancer by competitive enzyme-linked immunosorbent assay (ELISA) that allows a detectable sensitivity of 300 ng/mL. The results were obtained referring to a standard curve consisting in varying concentrations of human purified M6P/IGF2-R. Women sera consisted of cancer-free sera (n=39) or serum from women with breast cancer (n=39) were preincubated with anti-M6P/IGF2-R immunoglobulin Y (IgY) antibodies. High levels of M6P/IGF2-R (p<0.01) were found in serum from women with breast cancer in comparison with cancer-free serum. Overall the results support the hypothesis of increased release of the receptor from cancer cells to the blood and add one more argument for M6P/IGF2-R studying as a potential breast cancer marker.   Key words: Mannose-6-Phosphate/Insulin-like Growth Factor-2 Receptor (M6P/IGF2-R), loss of heterozygosity (LOH), suppressor gene, breast cancer, competitive enzyme-linked immunosorbent assay (ELISA), IgY, biological marker.
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乳腺癌患者血清甘露糖-6-磷酸/胰岛素样生长因子2受体(M6P/IGF2-R)水平升高
多功能跨膜甘露糖-6-磷酸/胰岛素样生长因子-2受体(M6P/IGF2-R)已被提出作为乳腺癌的推定预后标志物。杂合性缺失(LOH)与剩余等位基因的突变已在基因水平上被描述。我们之前报道过肿瘤细胞中M6P/IGF2-R蛋白水平明显低于正常乳腺肿瘤瘤周导管,这可能表明该受体从细胞膜向血液的释放增加。为了评估这一假设,我们在本研究中采用竞争性酶联免疫吸附试验(ELISA)测量了乳腺癌妇女血清中M6P/IGF2-R水平,检测灵敏度为300 ng/mL。根据不同浓度的人纯化M6P/IGF2-R组成的标准曲线获得结果。将无癌妇女血清(n=39)或乳腺癌妇女血清(n=39)与抗m6p /IGF2-R免疫球蛋白Y (IgY)抗体预先孵育。乳腺癌患者血清中M6P/IGF2-R水平高于无癌患者血清(p<0.01)。总的来说,这些结果支持了M6P/IGF2-R受体从癌细胞向血液释放增加的假设,并为M6P/IGF2-R作为潜在乳腺癌标志物的研究增加了一个论据。关键词:甘露糖-6-磷酸/胰岛素样生长因子-2受体(M6P/IGF2-R),杂合性缺失(LOH),抑制基因,乳腺癌,竞争性酶联免疫吸附试验(ELISA), IgY,生物标志物
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