MUC1 alters oncogenic events and transcription in human breast cancer cells.
MUC1 alters oncogenic events and transcription in human breast cancer cells.
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DOI：
10.1186/bcr1515
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Gendler SJ
中科院分区：
文献类型：
--
作者：
Hattrup CL;Gendler SJ
MUC 1是一种癌蛋白，其过表达与肿瘤的侵袭性和癌症患者的存活率低相关。MUC 1的许多致癌作用被认为是通过其胞质尾区与信号分子的相互作用而发生的。作为一种具有致癌功能的蛋白质，MUC 1与增殖、凋亡、侵袭和转录的调节有关。为了阐明MUC 1在癌症中的作用，我们用针对MUC 1的小干扰（si）RNA转染两种乳腺癌细胞系（MDA-MB-468和BT-20），并分析转录应答和致癌事件（增殖、凋亡和侵袭）。MUC 1 siRNA转染后，几个基因的转录发生了改变，包括MAP 2K 1（MEK 1）、JUN、PDGFA、CDC 25 A、VEGF和ITGAV（整合素αv）减少，TNF、RAF 1和MMP 2增加。在蛋白质水平上观察到其他变化，如c-Myc表达增加，AKT磷酸化增强，MEK 1/2和ERK 1/2活化降低。这些与细胞事件相关，因为MDA-MB-468系中的MUC 1 siRNA降低了增殖和侵袭，并增加了应激诱导的凋亡。有趣的是，无论siRNA如何，BT-20细胞显示出相似的凋亡水平，并且在MUC 1 siRNA后实际上增加了增殖。这些结果进一步增加了对MUC 1在转录中作用的认识，并表明MUC 1在乳腺癌中的调节可能比以前认识的更复杂。这两种细胞系之间的差异强调了在分析MUC 1的致癌功能时理解细胞特异性信号传导事件的背景的重要性，并警告不要在没有在完整生物系统中充分确认的情况下概括单个细胞系的结果。
MUC1 is an oncoprotein whose overexpression correlates with aggressiveness of tumors and poor survival of cancer patients. Many of the oncogenic effects of MUC1 are believed to occur through interaction of its cytoplasmic tail with signaling molecules. As expected for a protein with oncogenic functions, MUC1 is linked to regulation of proliferation, apoptosis, invasion, and transcription. To clarify the role of MUC1 in cancer, we transfected two breast cancer cell lines (MDA-MB-468 and BT-20) with small interfering (si)RNA directed against MUC1 and analyzed transcriptional responses and oncogenic events (proliferation, apoptosis and invasion). Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin αv), and increased TNF, RAF1, and MMP2. Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2. These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis. Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA. These results further the growing knowledge of the role of MUC1 in transcription, and suggest that the regulation of MUC1 in breast cancer may be more complex than previously appreciated. The differences between these two cell lines emphasize the importance of understanding the context of cell-specific signaling events when analyzing the oncogenic functions of MUC1, and caution against generalizing the results of individual cell lines without adequate confirmation in intact biological systems.
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影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
8
作者：
Al Masri, A;Gendler, SJ
通讯作者：
Gendler, SJ
影响因子：
3.6
作者：
Li, XJ;Wang, L;Offner, GD
通讯作者：
Offner, GD
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影响因子：
7.8
作者：
Lindqvist, Arne;Kallstrom, Helena;Lundgren, Andreas;Barsoum, Emad;Rosenthal, Christina Karlsson
通讯作者：
Rosenthal, Christina Karlsson
影响因子：
4
作者：
Carraway, KL;Ramsauer, VP;Carraway, CAC
通讯作者：
Carraway, CAC