Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines.
Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines.
复制标题
DOI：
10.1083/jcb.118.5.1213
复制
发表时间：
1992-09
期刊：
影响因子：
--
通讯作者：
Sager R
中科院分区：
文献类型：
--
作者：
Lee SW;Tomasetto C;Paul D;Keyomarsi K;Sager R
选择在正常人乳腺上皮细胞（NMECs）中表达而不在乳腺肿瘤细胞系（TMECs）中表达的mrna，进行减法杂交，克隆了人类间隙连接基因connexin 26 (Cx26)，其序列与大鼠基因相似。来自单个基因的两个Cx26转录本在nmec中表达，但在一系列tmec中均不表达。使用大鼠Cx探针的Northern分析显示，Cx43 mRNA在正常细胞中也表达，但在所检查的肿瘤细胞系中不表达。连接蛋白基因Cx31.1、Cx32、Cx33、Cx37和Cx40在正常细胞和肿瘤细胞系中均不表达。在细胞-细胞通讯研究中，正常细胞转移了路西法黄，而肿瘤细胞没有表现出染料转移。Cx26和Cx43蛋白在正常细胞中免疫定位到膜位点，但在肿瘤细胞中未发现。进一步分析表明，Cx26是一个细胞周期调控基因，在G1和S期间表达水平中等，在S晚期和G2强烈上调，这在洛伐他汀同步的nmec中得到证实。相反，Cx43在整个细胞周期中以一致的低水平组成性表达。用5dB-cAMP、维甲酸、冈田酸、雌二醇、TGFb等一系列药物治疗正常细胞和肿瘤细胞，对肿瘤细胞无连接蛋白诱导作用。然而，在一些tmes中，PMA诱导了两个Cx26转录本的重新表达，而不是Cx43的重新表达。因此，Cx26和Cx43在肿瘤细胞中均下调，但对某些信号的反应不同。通过药物治疗来调节间隙连接活性可能在癌症的临床治疗中有重要的应用。
Subtractive hybridization, selecting for mRNAs expressed in normal human mammary epithelial cells (NMECs) but not in mammary tumor cell lines (TMECs), led to the cloning of the human gap junction gene connexin 26 (Cx26), identified by its sequence similarity to the rat gene. Two Cx26 transcripts derived from a single gene are expressed in NMECs but neither is expressed in a series of TMECs. Northern analysis using rat Cx probes showed that Cx43 mRNA is also expressed in the normal cells, but not in the tumor lines examined. Connexin genes Cx31.1, Cx32, Cx33, Cx37, and Cx40 are not expressed in either normal cells or the tumor lines examined. In cell-cell communication studies, the normal cells transferred Lucifer yellow, while tumor cells failed to show dye transfer. Both Cx26 and Cx43 proteins were immunolocalized to membrane sites in normal cells but were not found in tumor cells. Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up- regulated in late S and G2, as shown with lovastatin-synchronized NMECs. Cx43, on the contrary is constitutively expressed at a uniform low level throughout the cell cycle. Treatment of normal and tumor cells with a series of drugs: 5dB-cAMP, retinoic acid, okadaic acid, estradiol, or TGFb had no connexin-inducing effect in tumor cells. However, PMA induced re-expression of the two Cx26 transcripts but not of Cx43 in several TMECs. Thus Cx26 and Cx43 are both downregulated in tumor cells but respond differentially to some signals. Modulation of gap-junctional activity by drug therapy may have useful clinical applications in cancer.
登录
查看更多内容
影响因子：
56.9
作者：
WEINBERG, RA
通讯作者：
WEINBERG, RA
影响因子：
7.5
作者：
Musil, L. S.;Goodenough, D. A.
通讯作者：
Goodenough, D. A.
DOI：
10.1073/pnas.81.7.2194
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAVIS, MM;COHEN, DI;HOOD, L
通讯作者：
HOOD, L
DOI：
10.1073/pnas.89.6.2504
发表时间：
1992-03-15
影响因子：
11.1
作者：
LEE, SW;TOMASETTO, C;SAGER, R
通讯作者：
SAGER, R
影响因子：
7.8
作者：
Musil, L S;Goodenough, D A
通讯作者：
Goodenough, D A