Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53.

Aging
Katherine HemingerSteven J Berberich

Abstract

While half of all human tumors possess p53 mutations, inactivation of wild-type p53 can also occur through a variety of mechanisms that do not involve p53 gene mutation or deletion. Our laboratory has been interested in tumor cells possessing wild-type p53 protein and elevated levels of HdmX and/or Hdm2, two critical negative regulators of p53 function. In this study we utilized RNAi to knockdown HdmX or Hdm2 in MCF7 human breast cancer cells, which harbor wild-type p53 and elevated levels of HdmX and Hdm2 then examined gene expression changes and effects on cell growth.Cell cycle and growth assays confirmed that the loss of either HdmX or Hdm2 led to a significant growth inhibition and G1cell cycle arrest. Although the removal of overexpressed HdmX/2 appears limited to an anti-proliferative effect in MCF7cells, the loss of HdmX and/or Hdm2 enhanced cytotoxicity in these same cells exposed to DNA damage. Through the use of Affymetrix GeneChips and subsequent RT-qPCR validations, we uncovered a subset of anti-proliferative p53 target genes activated upon HdmX/2 knockdown. Interestingly, a second set of genes, normally transactivated by E2F1 as cells transverse the G1-S phase boundary, were found repressed in a p21-dependent mann...Continue Reading

References

Sep 1, 1997·Frontiers in Bioscience : a Journal and Virtual Library·K Y Chen
Jul 29, 1998·Molecular Medicine Today·M H Kubbutat, K H Vousden
Apr 2, 1999·Seminars in Cancer Biology·W S el-Deiry
Oct 19, 2001·EMBO Reports·R StadA G Jochemsen
Dec 12, 2001·Nature Cell Biology·Thomas G HofmannM Lienhard Schmitz
Jan 10, 2002·Nature Cell Biology·Gabriella D'OraziSilvia Soddu
Aug 3, 2002·Nature Reviews. Cancer·Karen H Vousden, Xin Lu
Feb 4, 2003·Nature Reviews. Cancer·Patrick Chène
Sep 21, 2006·Molecular Cancer Therapeutics·Eveline BarbieriJason M Shohet
Nov 28, 2006·Nature Reviews. Cancer·Franck Toledo, Geoffrey M Wahl

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Citations

Aug 21, 2010·Cell Cycle·Kelly R MillerSteven J Berberich
Jun 15, 2011·International Journal of Cancer. Journal International Du Cancer·Rebecca TuttleSteven J Berberich
Jul 17, 2015·Cell Death & Disease·S HauptY Haupt
Oct 20, 2018·Journal of Biological Research·Vasiliki ChondrouNikos A Demopoulos
Jan 27, 2011·Annals of Surgical Oncology·Rebecca TuttleSteven J Berberich
Apr 15, 2010·Cancer Research·Kevin D KelleySteven J Berberich
Apr 20, 2019·Cancer Research·Jennifer HülleinThorsten Zenz

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Methods Mentioned

BETA
ubiquitination
transfection
flow cytometry
transfections
chip
PCR

Software Mentioned

GeneSpring GX
GeneChip
GCRMA

Related Concepts

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