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Beryllium sulfate induces p21 CDKN1A expression and a senescence-like cell cycle arrest in susceptible cancer cell types
| Content Provider | PubMed Central |
|---|---|
| Author | Gorjala, Priyatham Gary, Ronald K. |
| Copyright Year | 2010 |
| Abstract | In fibroblasts, beryllium salt causes activation of the p53 transcription factor and induction of a senescence-like state. It is not known whether Be2+ can affect the proliferation of cancer cells, which are generally unsusceptible to senescence. A172 glioblastoma and RKO colon carcinoma cell lines each have wildtype p53, so these cell types have the potential to be responsive to agents that activate p53. In A172 cells, BeSO4 produced a G0/G1-phase cell cycle arrest and increased expression of senescence-associated β-galactosidase, an enzymatic marker of senescence. BeSO4 caused phosphorylation of serine-15 of p53, accumulation of p53 protein, and expression of p21, the cyclin-dependent kinase inhibitor that is prominent during senescence. BeSO4 inhibited A172 growth with an IC50 = 4.7 µM in a 6-day proliferation assay. In contrast, BeSO4 had no effect on RKO cells, even though Be2+ uptake was similar for the two cell types. This differential responsiveness marks BeSO4 as a reagent capable of activating a separable branch of the p53 signaling network. A172 and RKO cells are known to exhibit p53-dependent upregulation of p21 in response to DNA damage. The RKO cells produced high levels of p21 when exposed to DNA damaging agents, yet failed to express p21 when treated with BeSO4. Conversely, BeSO4 did not cause DNA damage in A172 cells, yet it was a potent inducer of p21 expression. These observations indicate that the growth control pathway affected by BeSO4 is distinct from the DNA damage response pathway, even though both ultimately converge on p53 and p21. |
| Related Links | http://dx.doi.org/10.1007/s10534-010-9352-y |
| Ending Page | 1073 |
| Page Count | 13 |
| Starting Page | 1061 |
| File Format | |
| ISSN | 09660844 |
| e-ISSN | 15728773 |
| Journal | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine |
| Issue Number | 6 |
| Volume Number | 23 |
| Language | English |
| Publisher Date | 2010-12-01 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Metals and Alloys Biomaterials Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences |
