Anti-apoptotic proteins induce non-random genetic alterations that result in selecting breast cancer metastatic cells.

摘要: To shed light on the relationships between over-expression of anti-apoptotic proteins, genomic instability, and metastatic ability breast cancer cells, we analyzed genetic changes in tumors metastases by orthotopically injecting MDA-MB 435 cells transfected with genes Bcl-xL or Bcl-2 into nude mice. Tumors metastasis variants were extracted primary culture from breast, bone, lung, lymph node mice 435/Bcl-xL, 435/Bcl-2, 435/Neo tumors. Using Arbitrarily Primed Polymerase Chain Reaction (AP-PCR), which permits detection allelic imbalances, generated four different fingerprints utilizing primers. We found that damage fraction (GDF) increased 435/Bcl-2 (GDF=0.55) 435/Bcl-xL (GDF=0.34), regard to control (GDF=0.29), indicating non-random alterations occurred secondary over-expression. Anti-apoptotic proteins render susceptible vivo acquisition highly tumorigenic (Kruskal–Wallis, P=0.019) P=0.004) activity. therefore propose instability is a molecular mechanism favored involved selection during tumorigenesis, pathogenic event favoring expansion metastasis.