FUNCTIONAL EVIDENCE FOR A BREAST-CANCER GROWTH SUPPRESSOR GENE ON CHROMOSOME-17
FUNCTIONAL EVIDENCE FOR A BREAST-CANCER GROWTH SUPPRESSOR GENE ON CHROMOSOME-17
复制标题
DOI：
10.1093/hmg/2.11.1921
复制
发表时间：
1993-11-01
影响因子：
3.5
通讯作者：
STANBRIDGE, EJ
中科院分区：
文献类型：
--
作者：
CASEY, G;PLUMMER, S;STANBRIDGE, EJ
17号染色体的重排或缺失是乳腺肿瘤中最常见的遗传变化。分子分析表明，除了17p13.1上的p53基因外，17号染色体上可能至少有三个其他肿瘤抑制基因参与乳腺癌。在乳腺肿瘤中17 p13.3和17 q12-qter的杂合性缺失（洛）区域是常见的，遗传连锁分析将BRCA-1基因定位于17 q21。在这里，我们提供了生物学证据的17号染色体上的生长抑制基因的存在，导致在体外生长抑制p53野生型MCF 7乳腺癌细胞系。我们用微细胞介导的染色体转移法（MMCT）将一条正常的17号染色体导入MCF 7细胞，并证明细胞在10 ~ 12个群体倍增期前生长停滞。相反，正常染色体13的引入对这些细胞在体外或体内的生长没有影响。这些数据为17号染色体上存在生长抑制基因提供了直接的功能证据，该基因不是p53，并且可能代表在乳腺癌发展中起关键作用的几个基因之一。
Rearrangements or deletions of chromosome 17 are the most frequently observed genetic changes identified in breast tumors. Molecular analyses suggest that in addition to the p53 gene on 17p13.1 there may be at least three other tumor suppressor genes on chromosome 17 involved in breast cancer. Regions of loss of heterozygosity (LOH) identified on 17p13.3 and 17q12-qter occur frequently in breast tumors, and the BRCA-1 gene has been mapped to 17q21 by genetic linkage analysis. Here we provide biological evidence for the presence of a growth suppressor gene(s) on chromosome 17 that results in the in vitro growth suppression of the p53 wild-type MCF 7 breast cancer cell line. We have introduced a normal chromosome 17 into MCF 7 cells by microcell-mediated chromosome transfer (MMCT), and demonstrate that cells growth arrest before 10 to 12 population doublings. In contrast, the introduction of a normal chromosome 13 had no effect upon growth of these cells either in vitro or in vivo. These data provide direct functional evidence for the presence of a growth suppressor gene(s) on chromosome 17, which is not p53, and which may represent one of several gene(s) that play a critical role in the development of breast cancer.