Suppression of MDA-MB-435 breast carcinoma cell metastasis following the introduction of human chromosome 11.

Suppression of MDA-MB-435 breast carcinoma cell metastasis following the introduction of human chromosome 11.
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发表时间:
1996-03
期刊:
影响因子:
11.2
通讯作者:
Karen K. Phillips;Danny R. Welch;M. Miele;Jeong Hyung Lee;Lisa L. Wei;Bernard E Weissman
Karen K. Phillips;Danny R. Welch;M. Miele;Jeong Hyung Lee;Lisa L. Wei;Bernard E Weissman
中科院分区:
医学1区
文献类型:
--
作者:
Karen K. Phillips;Danny R. Welch;M. Miele;Jeong Hyung Lee;Lisa L. Wei;Bernard E Weissman

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为了确定11号染色体上的遗传信息在转移性乳腺肿瘤发生中的相关性,我们通过微细胞介导的染色体转移技术将正常人11号染色体导入高转移的MDA-MB-435乳腺癌细胞系。尽管MDA-MB-435受体细胞系和四个随机选择的微细胞杂交瘤克隆在裸鼠体内仍具有致瘤性,但杂交瘤细胞在肺和区域淋巴结转移方面的抑制率为95%(p<0.01)。我们还测试了6号染色体是否含有乳腺癌转移抑制基因,就像之前在人类黑色素瘤中观察到的那样。组合在一起,与转移能力较弱的亚克隆亲本细胞系mda-MB-453.7相比,四个新6微细胞杂交系在肺或淋巴结转移的发生率或数量上没有统计上的显著降低。已知的转移抑制基因nm23-H1(NME1)在该乳腺癌细胞系中的表达与微细胞杂交中的转移抑制无关。这些结果进一步表明,转移的控制与肿瘤的形成潜力在分子上是不同的。他们还指出,11号染色体编码了人类乳腺癌的转移抑制基因。
To determine the relevance of genetic information on chromosome 11 in the development of metastatic breast tumors, we introduced a normal human chromosome 11 into the highly metastatic MDA-MB-435 breast carcinoma cell line via the microcell-mediated chromosome transfer technique. Although the MDA-MB-435 recipient cell line and four randomly selected microcell hybrid clones remained tumorigenic in nude mice, the hybrids were >95% suppressed for metastasis to lung and regional lymph nodes (p<0.01). We also tested whether chromosome 6 harbors a metastasis-suppressor gene for breast cancer as observed previously for human melanoma. Grouped together, the four neo6 microcell hybrids had no statistically significant reduction in the incidence or number of lung or lymph node metastases compared to the weakly metastatic, subcloned parent cell line, MDA-MB-453.7. Expression of nm23-H1 (NME1), a known metastasis-suppressor gene in this breast cancer cell line, did not correlate with metastasis suppression in the microcell hybrids. These results further demonstrate that control of metastasis is molecularly distinct from tumorigenic potential. They also indicate that chromosome 11 encodes a metastasis-suppressor gene for human breast cancer.