Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, PR, Brazil.
Cytokine. 2011 Aug;55(2):260-5. doi: 10.1016/j.cyto.2011.04.017. Epub 2011 May 17.
The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.
趋化因子的作用在癌症风险和肿瘤进展中都得到了广泛的分析。在不同的细胞因子中，CXCR4 及其配体 CXCL12 最近受到了更密切的关注。在乳腺癌患者中，评估了 CXCL12 基因中的单核苷酸多态性 (SNP) rs1801157（以前称为 CXCL12-A/SDF1-3'A）和外周血中 mRNA CXCL12 的相对表达，因为趋化因子 CXCL12 和其受体 CXCR4 调节白细胞的迁移和许多重要的生物学过程，包括肿瘤生长、血管生成和不同类型肿瘤的转移。通过聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 使用 MspI 限制性内切酶进行基因分型，通过定量 RT-PCR 进行表达分析。在乳腺癌患者和健康献血者之间，以及在不同肿瘤分期的患者中评估 CXCL12 mRNA 表达时，均未观察到 GG 基因型和等位基因 A 携带者频率的差异。然而，当根据 CXCL12 rs1801157 等位基因 A 的存在与否分析乳腺癌患者的 CXCL12 mRNA 相对表达时，观察到了显著差异。携带等位基因 A 的乳腺癌患者的 mRNA CXCL12 表达约为 GG 乳腺癌患者的 2.1 倍小。携带 CXCL12 等位基因 A 的雌激素阳性患者在外周血中的 CXCL12 表达明显低于 GG 激素阳性患者 (p=0.039)。我们的研究结果表明，等位基因 A 与 ER 阳性乳腺癌患者外周血中 CXCL12 的低表达相关，这表明对乳腺癌临床结果有影响。
