Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.
Understanding the role of keratins 8 and 18 in neoplastic potential of breast cancer derived cell lines.
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DOI：
10.1371/journal.pone.0053532
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Vaidya MM
中科院分区：
文献类型：
--
作者：
Iyer SV;Dange PP;Alam H;Sawant SS;Ingle AD;Borges AM;Shirsat NV;Dalal SN;Vaidya MM
乳腺癌是一种复杂的疾病，不能仅仅通过临床参数（如淋巴结累及和组织学分级）来定义，也不能通过常规的生物标志物（如雌激素受体（ER）、孕激素受体（PGR）和表皮生长因子受体2 (HER2)）来诊断和预后。乳腺癌起源于上皮细胞。角蛋白(K)是上皮细胞的细胞质中间丝蛋白，在乳腺恶性转化过程中，角蛋白的表达模式发生了变化。K8/18对在乳腺上皮腔细胞中表达，但其在乳腺癌预后中的作用尚不清楚。在这项研究中，我们调节了K8的表达，以了解K8/18对在三种不同的乳腺上皮来源细胞系中的作用：未转化的MCF10A，转化但侵袭性差的MDA MB 468和高度侵袭性的MDA MB 435。K8在侵袭性MDA MB 435细胞系中的上调，导致其增殖、活力、体外侵袭、肿瘤体积和肺转移显著降低。MDA - MB 468中K8的下调导致MCF10A细胞转化电位、运动性和侵袭性显著增加，而MCF10A细胞转化实验未显示出任何变化。这些结果表明K8/18在调节乳腺癌侵袭中的作用——它的存在与低侵袭性表型相关，而不存在与高侵袭性、去分化表型相关。这些数据可能对乳腺癌的预后有重要意义。
Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood. In this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays. These results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer.
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影响因子：
4
作者：
Alam, Hunain;Kundu, Samrat T.;Vaidya, Milind M.
通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
7.8
作者：
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通讯作者：
Melton, DW
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影响因子：
3.3
作者：
Alam H;Sehgal L;Kundu ST;Dalal SN;Vaidya MM
通讯作者：
Vaidya MM