Beyer Sasha J, Zhang Xiaoli, Jimenez Rafael E, Lee Mei-Ling T, Richardson Andrea L, Huang Kun, Jhiang Sissy M
Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio 43210, USA.
BMC Res Notes. 2011 Oct 11;4:397. doi: 10.1186/1756-0500-4-397.
Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated.
Published oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified.
NIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype.
Further investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.
钠/碘同向转运体（NIS）介导的碘摄取使放射性碘可用于甲状腺癌治疗。NIS在乳腺肿瘤中也有表达，这为乳腺癌的放射性核素治疗带来了可能性。然而，大多数乳腺癌中NIS表达较低，可能不足以用于放射性核素治疗。我们旨在确定与NIS表达相关的生物标志物，以便阐明人类乳腺肿瘤中NIS调节的潜在机制。
分析美国国立生物技术信息中心基因表达综合数据库中已发表的寡核苷酸微阵列数据，以确定人类乳腺肿瘤中与NIS mRNA水平紧密相关的基因表达。在一个由28个人类乳腺肿瘤组成的组织微阵列中进行NIS免疫染色，每个肿瘤都有相应的寡核苷酸微阵列数据，从而可以确定与细胞表面NIS蛋白水平相关的基因表达。
当通过Affymetrix寡核苷酸微阵列平台检测时，乳腺肿瘤之间或与正常乳腺组织相比，NIS mRNA水平没有差异。细胞表面NIS蛋白水平比其相应的NIS mRNA水平变化更大。尽管检测的乳腺肿瘤数量有限，但我们的分析确定半胱氨酰-tRNA合成酶是一种生物标志物，它与雌激素受体阳性乳腺癌亚型中的细胞表面NIS蛋白水平高度相关。
对每个乳腺癌分子亚型中与细胞表面NIS蛋白水平相关基因的进一步研究，可能会为在一部分乳腺癌患者中选择性增加NIS表达/功能带来新的靶点。
