API

Event: 1504

Key Event Title

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p21 (CDKN1A) expression, increase

Short name

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p21 (CDKN1A) expression, increase

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action
positive regulation of gene expression cyclin-dependent kinase inhibitor increased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Life Stages

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Life stage Evidence
Not Otherwise Specified Moderate

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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p21 (CDKN1A; cyclin dependent kinase inhibitor 1A) binds to and inhibits the activity of cyclin-dependent kinase 2 or cyclin-dependent kinase 4 complexes, and regulates cell cycle progression in G1 phase. p21 is important for cell cycle regulation.


How It Is Measured or Detected

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The p21 mRNA is measured with real-time RT-PCR technique using primers for p21 [Dayan, 2014]. Gene expression of p21 is measured with microarray technique using gene chips after cDNA preparation from total RNA extracted from the samples [Glaser, 2003, Hoshino, 2007]. Protein level of p21 is measured with Western blot analysis using anti-p21 antibody [Parajuli, 2014, Glaser, 2003].


Domain of Applicability

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The p21 up-regulation by HDIs is well conserved between species from lower organism to mammals.

・FK228, a HDAC inhibitor, up-regulated p21 level in human esophageal cancer TE2 cells (Homo sapiens) [Hoshino, 2007].

・MAA, a HDAC inhibitor, induced p21 up-regulation in human prostate cancer cell lines (Homo sapiens) [Parajuli, 2014].

・MAA increases p21 expression in human bladder carcinoma cells, T24 (Homo sapiens) [Glaser, 2003].

・MAA up-regulated p21 expression in limbs of CD1 embryonic mice (Mus musculus) [Dayan, 2014].


References

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Dayan C and Hales BF. (2014) Effects of ethylene glycol monomethyl ether and its metabolite, 2-methoxyacetic acid, on organogenesis stage mouse limbs in vitro. Birth Defects Res (Part B) 101:254-261

Glaser KB et al. (2003) Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol Cancer Ther 2:151-163

Hoshino I et al. (2007) Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells. Oncol Rep 18:585-592

Parajuli KR et al. (2014) Methoxyacetic acid suppresses prostate cancer cell growth by inducing growth arrest and apoptosis. Am J Clin Exp Urol 2:300-313