Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells

Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells
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DOI:
10.1002/ijc.10470
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发表时间:
2002-07-10
影响因子:
6.4
通讯作者:
Newsham, IF
Newsham, IF
中科院分区:
医学1区
文献类型:
--
作者:
Charboneau, AL;Singh, V;Newsham, IF

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肺腺癌(DAL-1)基因的差异表达与4.1/ezrin/radixin/moesin/神经纤维瘤病2 (ERM/NF2)蛋白家族成员具有显著的同源性,先前已被证明可抑制肺癌细胞系的生长。该基因定位于18p11.3染色体带,该染色体带在非小细胞肺癌和乳腺导管原位癌(DCIS)中发生杂合性缺失(LOH)。这一发现表明,该染色体区域内基因(可能是DAL-1)的改变在乳腺疾病进展的早期可能是重要的。我们构建了组成或在诱导启动子控制下表达DAL-1的MCF-7细胞系,并分析了DAL-1表达对生长的影响。这些研究表明DAL-1蛋白抑制MCF-7细胞的生长,可能部分通过诱导细胞凋亡来实现。此外,DAL-1的表达增加了这些细胞对各种细胞外基质的附着。这是首次证明DAL-1蛋白在细胞粘附和凋亡之间的界面上起着控制细胞生长的作用。(C) 2002 Wiley-Liss, Inc。
The differentially expressed in adenocarcinoma of the lung (DAL-1) gene, which shares significant homology with members of the 4.1/ezrin/radixin/moesin/neurofibromatosis 2 (ERM/NF2) protein family, has previously been shown to suppress growth in lung cancer cell lines. This gene localizes to chromosome band 18p11.3, which undergoes loss of heterozygosity (LOH) in nonsmall cell lung carcinomas and a significant proportion of ductal carcinomas in situ (DCIS) of the breast. This finding suggests that alteration of gene(s) (possibly DAL-1) within this chromosomal region may be important early in the progression of breast disease. We generated MCF-7 cell lines expressing DAL-1 constitutively or under the control of an inducible promoter and analyzed the effect of DAL-1 expression on growth. These investigations revealed that the DAL-1 protein suppresses the growth of MCF-7 cells and may do so in part through the induction of apoptosis. In addition, expression of DAL-1 increased attachment of these cells to a variety of extracellular matrices. This is the first evidence that the DAL-1 protein functions at the interface between cell adhesion and apoptosis in controlling cell growth. (C) 2002 Wiley-Liss, Inc.