Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer.
Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer.
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DOI：
10.1007/s00109-008-0409-0
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发表时间：
2009-01
影响因子：
4.7
通讯作者：
Birkenkamp-Demtroder, Karin
中科院分区：
文献类型：
--
作者：
Mansilla, Francisco;da Costa, Kerry-Ann;Wang, Shuli;Kruhoffer, Mogens;Lewin, Tal M.;Orntoft, Torben F.;Coleman, Rosalind A.;Birkenkamp-Demtroder, Karin
关键词：
胆碱代谢物谱的改变是癌细胞的一个公认的特征。在结直肠癌（CRC）中，磷脂酰胆碱是最重要的磷脂。在本研究中，我们报道了溶血磷脂酰胆碱酰基转移酶1 (LPCAT1; NM_024830.3)，一种将溶血磷脂酰胆碱转化为磷脂酰胆碱的酶，与正常粘膜相比，在结直肠癌中高度过表达。我们的微阵列转录谱研究显示，与10个正常粘膜相比，168个结直肠腺癌中转录物过表达显著（p<10−8）。用LPCAT1多克隆抗体对结肠肿瘤进行免疫组化分析，证实了LPCAT1蛋白的上调。COS7细胞中LPCAT1的过表达使该蛋白定位于内质网和线粒体，使LPCAT1的特异性活性增加38倍。在培养细胞中，过表达的LPCAT1增强了[14C]棕榈酸酯与磷脂酰胆碱的结合。转染LPCAT1的COS7细胞的生长速率没有变化，而结肠癌细胞系SW480的生长速率显著（p<10−5）提高了17%。我们得出结论，LPCAT1可能通过磷脂酰胆碱重塑促进总胆碱代谢物的积累，从而改变结直肠癌的脂质谱，这是恶性肿瘤的一个特征。
The alteration of the choline metabolite profile is a well-established characteristic of cancer cells. In colorectal cancer (CRC), phosphatidylcholine is the most prominent phospholipid. In the present study, we report that lysophosphatidylcholine acyltransferase 1 (LPCAT1; NM_024830.3), the enzyme that converts lysophosphatidylcholine into phosphatidylcholine, was highly overexpressed in colorectal adenocarcinomas when compared to normal mucosas. Our microarray transcription profiling study showed a significant (p<10−8) transcript overexpression in 168 colorectal adenocarcinomas when compared to ten normal mucosas. Immunohistochemical analysis of colon tumors with a polyclonal antibody to LPCAT1 confirmed the upregulation of the LPCAT1 protein. Overexpression of LPCAT1 in COS7 cells localized the protein to the endoplasmic reticulum and the mitochondria and increased LPCAT1 specific activity 38-fold. In cultured cells, overexpressed LPCAT1 enhanced the incorporation of [14C]palmitate into phosphatidylcholine. COS7 cells transfected with LPCAT1 showed no growth rate alteration, in contrast to the colon cancer cell line SW480, which significantly (p<10−5) increased its growth rate by 17%. We conclude that LPCAT1 may contribute to total choline metabolite accumulation via phosphatidylcholine remodeling, thereby altering the CRC lipid profile, a characteristic of malignancy.
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DOI：
10.1073/pnas.0604946103
发表时间：
2006-08-01
影响因子：
11.1
作者：
Chen, Xueni;Hyatt, Brian A.;Shannon, John M.
通讯作者：
Shannon, John M.
DOI：
10.1016/s0006-291x(02)00920-8
发表时间：
2002-08-23
影响因子：
3.1
作者：
Ramírez de Molina, A;Rodríguez-González, A;Lacal, JC
通讯作者：
Lacal, JC
影响因子：
4.8
作者：
Baburina, I;Jackowski, S
通讯作者：
Jackowski, S
影响因子：
11.2
作者：
Glunde, K;Jie, C;Bhujwalla, ZM
通讯作者：
Bhujwalla, ZM
影响因子：
7.4
作者：
Koc, H;Mar, MH;Zeisel, SH
通讯作者：
Zeisel, SH