PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas.

PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas.
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DOI:
10.1038/sj.bjc.6603926
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发表时间:
2007-09-17
影响因子:
8.8
通讯作者:
Arcaro, K. F.
Arcaro, K. F.
中科院分区:
医学1区
文献类型:
--
作者:
Gozgit, J. M.;Pentecost, B. T.;Marconi, S. A.;Ricketts-Loriaux, R. S. J.;Otis, C. N.;Arcaro, K. F.

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我们使用了人雌激素受体(ER)阳性的MCF - 7细胞系的一种新型变体TMX2 - 28作为研究乳腺癌的模型。TMX2 - 28细胞未检测到雌激素受体的mRNA或蛋白质表达水平,且表达基底细胞角蛋白(CKs)5、14和17。TMX2 - 28与其亲本细胞系MCF - 7之间的cDNA微阵列比较鉴定出1402个差异表达的转录本,其中之一是磷脂酶D1(PLD1)。通过实时逆转录 - 聚合酶链反应,我们证实TMX2 - 28细胞中PLD1的mRNA水平比MCF - 7细胞高10倍。接下来我们检测了人乳腺癌中PLD1的表达。在表达高水平基底细胞角蛋白5和/或17的mRNA的乳腺肿瘤中,磷脂酶D1的mRNA水平较高,但在雌激素受体阴性的肿瘤中,PLD1的mRNA水平并没有显著升高。通过免疫组化检测的42个乳腺肿瘤中有10个(24%)磷脂酶D1蛋白过表达。在31个雌激素受体阳性肿瘤中有6个以及11个雌激素受体阴性肿瘤中有4个磷脂酶D1过表达。在4个显示高CK5/17表达的肿瘤中有3个磷脂酶D1过表达。5个PLD1阳性肿瘤磷酸化 - Akt表达为阴性,但磷酸化 - 哺乳动物雷帕霉素靶蛋白(mTOR)表达为阳性。另外5个PLD1阳性乳腺肿瘤磷酸化 - Akt表达为阳性;然而,这些病例中只有2个磷酸化 - mTOR为阳性。在这项研究中,我们报道在一部分磷酸化 - Akt阴性的乳腺癌中PLD1和磷酸化 - mTOR共表达。
We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT–PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas.
DOI: 10.1016/j.cub.2003.11.021
发表时间: 2003-12-02
期刊: CURRENT BIOLOGY
影响因子: 9.2
作者:
Fang, YM;Park, IH;Chen, J
通讯作者: Chen, J
DOI: 10.1126/science.1066015
发表时间: 2001-11-30
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: Chen, J
DOI: 10.1016/j.taap.2003.12.003
发表时间: 2004-04-01
影响因子: 3.8
作者:
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通讯作者: Arcaro, KF
DOI: 10.1023/a:1006132427948
发表时间: 1998-01-01
影响因子: 3.8
作者:
Osborne, CK
通讯作者: Osborne, CK
DOI: 10.1038/sj.onc.1206565
发表时间: 2003-06-19
期刊: ONCOGENE
影响因子: 8
作者:
Chen, YH;Zheng, Y;Foster, DA
通讯作者: Foster, DA