A transcriptional repressor of osteopontin expression in the 4T1 murine breast cancer cell line.
A transcriptional repressor of osteopontin expression in the 4T1 murine breast cancer cell line.
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DOI：
10.1016/j.bbrc.2004.07.063
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发表时间：
2004-09
影响因子：
3.1
通讯作者：
Chengjiang Gao;Z. Mi;Hongtao Guo;Junping Wei;P. Wai;P. Kuo
中科院分区：
文献类型：
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作者：
Chengjiang Gao;Z. Mi;Hongtao Guo;Junping Wei;P. Wai;P. Kuo
骨桥蛋白（OPN）是一种由1298个氨基酸组成的高度亲水性、带负电荷的唾液酸蛋白，是肿瘤转移行为的重要介质。我们以前已经证明，内毒素依赖性骨桥蛋白基因转录受组成性转录抑制蛋白，异质核核糖核蛋白A/B（hnRNP-A/B）。然而，在癌症的背景下，hnRNP-A/B在OPN的转录调节及其促进转移功能中的作用尚未被研究。我们在4 T1小鼠乳腺上皮肿瘤细胞系中检测了hnRNP-A/B，4 T1小鼠乳腺上皮肿瘤细胞系是一种硫鸟嘌呤耐药亚系，与人类IV期乳腺癌非常相似。我们的数据表明，hnRNP-A/B p37与OPN启动子结合，显著降低OPN启动子活性和mRNA水平，消除OPN蛋白表达，并抑制OPN依赖的体外转移行为、运动性和侵袭相关性。这些结果是独特的，可能会提出新的治疗方法，以重新建立局部区域控制癌症。
Osteopontin (OPN) is a highly hydrophilic and negatively charged sialoprotein of ∼298 amino acids which is an important mediator of tumor metastatic behavior. We have previously demonstrated that endotoxin-dependent OPN gene transcription is regulated by a constitutive transcriptional repressor protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNP-A/B). However, in the context of cancer, the role of hnRNP-A/B in the transcriptional regulation of OPN and its metastasis-promoting functions has not been previously studied. We examined hnRNP-A/B in the 4T1 murine mammary epithelial tumor cell line, a thioguanine resistant subline which closely mimics stage IV breast cancer in humans. Our data indicate that hnRNP-A/B p37 binds to the OPN promoter, significantly decreases OPN promoter activity and mRNA levels, ablates OPN protein expression, and inhibits OPN dependent in vitro correlates of metastatic behavior, motility, and invasion. These results are unique and may suggest new therapies to re-establish loco-regional control of cancers.