Metastatic behavior of human breast carcinomas overexpressing the Bcl-x(L) gene: a role in dormancy and organospecificity.

Abstract

The ability of metastatic cells to survive antiapoptotic signals may contribute to the organospecific-spread patterns of clinical metastasis and dormancy. MDA-MB-435 breast cancer cells (435/Bcl-x(L)), which overexpress the Bcl-x(L) gene, were labeled with the luciferase gene and injected orthotopically into homozygous athymic Balb/c (nude) mice to study the metastatic behavior of the breast cancer cells. The overexpression of Bcl-x(L) in tumors increased the overall metastatic burden in mice (bones, liver, kidneys, brain, lungs, and lymph nodes) in comparison with control tumors (435/NEO:luc) during the same time interval (ANOVA, p = 0.005). The principal differences after 110 days were found in bones, which had 1.5 x 10(5) +/- 1.2 x 10(5) tumor cell equivalents (p = 0.03), and lymph nodes, which had 7.0 x 10(6) +/- 6.0 x 10(6) tumor cell equivalents (p = 0.08). The analyses of light production by tissues at different times showed that cells from 435/NEO:luc and 435/Bcl-x(L).luc tumors were detectable in several organs by the second day after intramammary fat pad implantation. Although initially arriving at the target organs in similar numbers, 435/Bcl-x(L) cells developed more metastases than 435/Neo cells, indicating that the Bcl-x(L) gene might have a role in breast cancer dormancy, promoting survival of cells in metastatic foci. Thus, we suggest that overexpression of Bcl-x(L) could counteract the proapoptotic signals in the microenvironment and favor the successful development of metastasis in specific organs.

• Authors: N Rubio, L España, Y Fernández, J Blanco, A Sierra
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 81 Issue 5 Pg. 725-34 (May 2001) ISSN: 0023-6837 [Print] United States
• PMID: 11351044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2L1 protein, human
• Bcl2l1 protein, mouse
• Proto-Oncogene Proteins c-bcl-2
• bcl-X Protein
• Luciferases

Topics

• Analysis of Variance
• Animals
• Apoptosis (genetics)
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Count
• Humans
• Luciferases (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis (genetics)
• Neoplasm Transplantation
• Organ Specificity
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics)
• Time Factors
• Transfection
• Tumor Cells, Cultured
• bcl-X Protein