NDLI: Beryllium sulfate induces p21CDKN1A expression and a senescence-like cell cycle arrest in susceptible cancer cell types

Content Provider	Springer Nature Link
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.
Starting Page	1061
Ending Page	1073
Page Count	13
File Format	PDF
ISSN	09660844
Journal	BioMetals
Volume Number	23
Issue Number	6
e-ISSN	15728773
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-06-12
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Beryllium sulfate Cell cycle arrest Senescence p53 Glioma Physical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Metals and Alloys Biochemistry, Genetics and Molecular Biology Biomaterials Agricultural and Biological Sciences

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