Words similar to anchorage-independent
Example sentences for: anchorage-independent
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As an alternative to the forced expression of ectopic PTEN in anchorage-independent, PTEN-negative tumor cells, our study has focused on the regulation of endogenous PTEN in anchorage-dependent mouse and human fibroblasts.
Previous studies by others had shown that the ectopic expression of PTEN in anchorage-independent tumor cells greatly reduced their ability to grow in soft agar [ 4 5 6 ] . In this latter situation, however, the forced expression of ectopic PTEN effectively impairs cellular proliferation in general, even under two-dimensional culture conditions where the cells are attached to substratum [ 4 6 7 8 9 10 18 33 44 ] . It was therefore difficult to discern from these experiments how effectively and selectively PTEN participates in anchorage-dependent growth control.
It should be noted that the fibroblast cells lines we used remain fully viable after detachment and transfer to suspension culture [ 31 43 ] . This is in contrast to most epithelial cells which undergo anoikis, i.e., apoptotic cell death after the disruption of cell-matrix interactions [ 45 ] . It is of interest that some anchorage-independent tumor cells, most of which are of epitheloid origin, become susceptible to anoikis after the introduction of exogenous PTEN [ 23 34 35 36 ] . These observations are in line with the established ability of PTEN to down-regulate the phosphatidylinositol 3-kinase (PI3-K)/PKB survival pathway [ 11 46 ] . The absence of anoikis in our two cell lines may reflect inherent cell type specific differences, i.e., the superior ability of fibroblasts to survive under suspension culture conditions.
In light of the close correlation between the anchorage-independent phenotype and the tumorigenicity of transformed cells, it is important to fully understand the cellular mechanisms that are involved in cell growth arrest after the disruption of cell-matrix interactions.
For example, mouse embryonal stem (ES) cells with homozygous deletion of the PTEN gene exhibit increased anchorage-independent growth as compared to normal ES cells [ 12 ] . Similarly, transfer of a wild type PTEN gene into anchorage-independent human glioblastoma cells (which lack functional PTEN), results in their greatly reduced ability to form colonies in soft agar [ 4 5 6 ] . The interpretation of these latter findings, however, is complicated by the strong anti-proliferative effects of PTEN even in monolayer culture, which is consistently observed when the wild type version of this gene is introduced into PTEN-negative tumor cells [ 4 6 7 8 9 10 18 33 ] . Moreover, in human glioma and breast cancer cell lines, the ectopic expression of wild type PTEN leads to anoikis, which is apoptosis initiated by the disruption of cell matrix-interactions [ 23 34 35 36 ] .
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