ASSOCIATION OF INCREASED BASEMENT-MEMBRANE INVASIVENESS WITH ABSENCE OF ESTROGEN-RECEPTOR AND EXPRESSION OF VIMENTIN IN HUMAN BREAST-CANCER CELL-LINES

ASSOCIATION OF INCREASED BASEMENT-MEMBRANE INVASIVENESS WITH ABSENCE OF ESTROGEN-RECEPTOR AND EXPRESSION OF VIMENTIN IN HUMAN BREAST-CANCER CELL-LINES
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DOI:
10.1002/jcp.1041500314
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发表时间:
1992-03-01
影响因子:
5.6
通讯作者:
DICKSON, RB
DICKSON, RB
中科院分区:
生物学2区
文献类型:
--
作者:
THOMPSON, EW;PAIK, SM;DICKSON, RB

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雌激素受体(ER)的缺乏和波形蛋白(VIM)的存在与人类乳腺癌预后不良有关。我们探索了ER、VIM和人类乳腺癌细胞系侵袭性之间的关系。在基质生长试验中,ER+/VIM- (MCF-7、T47D、ZR-75-1)和ER-/VIM- (MDA-MB-468、SK-Br-3)细胞系无侵袭性,而ER-/VIM+ (BT549、MDA-MB-231、MDA-MB-435、MDA-MB-436、Hs578T)细胞系形成侵袭性穿透性菌落。同样,在Boyden室化学侵袭试验中,ER-/VIM+细胞系的侵袭性明显高于ER+/VIM-或ER-/VIM-细胞系。裸鼠侵袭性活动仅见于ER-/VIM+细胞系MDA-MB-231、MDA-MB-435和MDA-MB-436。在5只小鼠中,1只小鼠的Hs578T细胞(ER-/VIM+)表现出向肺部的血液播散,但缺乏局部侵袭。ER-/VIM+ MCF-7ADR亚群在体外的活性明显高于MCF-7细胞,但在体内的活性与野生型MCF-7亲本相似。来自这些细胞系的数据表明,人类乳腺癌的进展首先导致ER的丧失,随后导致VIM的获得,后者通过增强侵袭性而增加转移潜力。MCF-7ADR数据提供的证据表明,这种转变可以发生在人类乳腺癌细胞中。Vimentin的表达可能为乳腺癌细胞的侵袭和/或进展机制提供有用的见解。
Lack of estrogen receptor (ER) and presence of vimentin (VIM) associate with poor prognosis in human breast cancer. We have explored the relationships between ER, VIM, and invasiveness in human breast cancer cell lines. In the matrigel outgrowth assay, ER+/VIM- (MCF-7, T47D, ZR-75-1), and ER-/VIM- (MDA-MB-468, SK-Br-3) cell lines were uninvasive, while ER-/VIM+ (BT549, MDA-MB-231, MDA-MB-435, MDA-MB-436, Hs578T) lines formed invasive, penetrating colonies. Similarly, ER-/VIM+ cell lines were significantly more invasive than either the ER+/VIM- or ER-/VIM- cell lines in the Boyden chamber chemoinvasion assay. Invasive activity in nude mice was only seen with ER-/VIM+ cell lines MDA-MB-231, MDA-MB-435 and MDA-MB-436. Hs578T cells (ER-/VIM+) showed hematogenous dissemination to the lungs in one of five mice, but lacked local invasion. The ER-/VIM+ MCF-7ADR subline was significantly more active than the MCF-7 cells in vitro, but resembled the wild-type MCF-7 parent in in vivo activity. Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness. The MCF-7ADR data provide evidence that this transition can occur in human breast cancer cells. Vimentin expression may provide useful insights into mechanisms of invasion and/or breast cancer cell progression.