Suppression of MDA-MB-435 breast carcinoma cell metastasis following the introduction of human chromosome 11.
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.
Phillips
K K
KK
Department of Pathology, Linberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA.
Welch
D R
DR
Miele
M E
ME
Lee
J H
JH
Wei
L L
LL
Weissman
B E
BE
D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D002459:Cell Fusion / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured