ESTABLISHMENT AND CHARACTERIZATION OF UM-EC-2, A TAMOXIFEN-SENSITIVE, ESTROGEN RECEPTOR-NEGATIVE HUMAN ENDOMETRIAL CARCINOMA CELL-LINE
ESTABLISHMENT AND CHARACTERIZATION OF UM-EC-2, A TAMOXIFEN-SENSITIVE, ESTROGEN RECEPTOR-NEGATIVE HUMAN ENDOMETRIAL CARCINOMA CELL-LINE
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DOI：
10.1016/0090-8258(90)90332-f
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发表时间：
1990-05-01
影响因子：
4.7
通讯作者：
CAREY, TE
中科院分区：
文献类型：
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作者：
GRENMAN, SE;WORSHAM, MJ;CAREY, TE
UM-EC-2来源于一例低分化IB期子宫内膜癌患者。该细胞系在裸鼠体内产生的肿瘤具有与患者肿瘤相同的组织学特征。UM-EC-2细胞表达。β。2微球蛋白、表皮生长因子受体（EGF）和H血型抗原。这种膜抗原表型与人类子宫内膜起源的细胞一致。UM-EC-2的核型相当复杂，重排影响除3、10、14、19和20染色体外的所有染色体。细胞有两个群体，一个超二倍体群体，模态数为53 ~ 55，一个超四倍体群体，模态数为109。根据单个染色体的拷贝数和重排，提出了四倍体化前后的假设序列。将UM-EC-2核型与UM-EC-1（先前描述的来自不同子宫内膜癌患者的细胞系）的核型进行比较，发现这两条细胞系有8个非常相似的染色体变化，包括4号染色体的大部分缺失、影响8p近端带的断点、9q的大部分缺失、12q22的断点、13q的缺失、18q近端带的断点和22p11的断点。这些变化可能代表低分化子宫内膜癌的非随机染色体异常。在原发肿瘤和细胞系中均未检测到雌激素（ER）和孕激素（PgR）受体。但在体外实验中，UM-EC-2细胞对他莫昔芬（TAM）的生长抑制非常敏感。1微摩尔TAM对细胞生长有50%的抑制作用，2.5 μ。M引起细胞抑制；M - TAM具有细胞毒性，暴露于药物5-7天后杀死所有细胞。矛盾的是，100 nM雌二醇（E2）引起了细胞生长的适度增加，但它并没有阻止或逆转TAM的生长抑制作用。这些发现支持了在某些肿瘤中TAM通过不依赖于er的机制导致生长抑制的概念。UM-EC-2细胞对EGF的生长调节也很敏感。因此，这些细胞提供了一种新的体外人子宫内膜癌模型，可以研究TAM和EGF作为生长调节物质的作用。
UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient''s tumor. UM-EC-2 cells express .beta.2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 .mu.M caused cytostasis, and 5 .mu.M TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.