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Journal of Mammary Gland Biology and Neoplasia

, Volume 16, Issue 3, pp 247–256 | Cite as

Oncogene-Induced Senescence and its Role in Tumor Suppression

  • Jay P. Reddy
  • Yi Li
Article

Abstract

While senescence has been known for some time as an inevitable result of repeated DNA replication, oncogene-induced senescence (OIS) represents a relatively new phenomenon. OIS, like apoptosis, has emerged to represent a putative barrier to tumorigenesis in many tissues, including the breast. Here we discuss signals that initiate OIS, evidence for its role in tumor suppression, and mechanisms for its evasion in tumorigenesis.

Keywords

Senescence Oncogene-induced senescence Breast cancer Anticancer barrier DDR 

Abbreviations

ADH

atypical ductal hyperplasias

ATM

ataxia telangiectasia mutated

ATR

ataxia telangiectasia and Rad3 related

CXCR2

chemokine receptor 2

Dcr2

decoy receptor 2

DDR

DNA Damage Response

DCIS

ductal carcinoma in situ

Dec1

differentiated embryo chondrocyte expressed gene 1

DSB

double-strand break

EMT

epithelial-mesenchymal transition

H3K9

histone H3 di- or tri-methylated on lysine 9

HMGA2

high mobility group protein A2

HP1γ

heterochromatin protein 1γ

IGFBP7

insulin-like growth factor-binding protein 7

IR

ionizing radiation

MMP3

matrix metalloproteinase 3

MMTV

mouse mammary tumor virus

MRN

MRE11-RAD50-NBS1

OIS

oncogene-induced senescence

PAI-1

plasminogen activator inhibitor-1

PIN

intraepithelial neoplasias

RCAS

replication competent ALV-LTR, splice receptor

RFC

replication factor C

ROS

reactive oxygen species

RPA

replication protein A

SAHF

senescence-associated heterochromatin foci

SASP

senescence-associated secretory phenotype

SSB

single-strand break

SA-β-Gal

senescence-associated β-galactosidase

TVA

tumor virus A

Notes

Acknowledgements

We thank Drs. Pumin Zhang and Gary Chamness for critical review of this manuscript. This work was supported in part by funds from USAMRMC BC030755 (to Y.L.) and BC073703 (to Y.L.) and from National Institutes of Health CA124820 (to Y.L.). J.P.R. was supported by the Robert and Janice McNair Foundation and a CDMRP pre-doctoral fellowship (BC083190).

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Molecular & Cellular BiologyBaylor College of MedicineHoustonUSA
  2. 2.Lester and Sue Smith Breast Center, Baylor College of MedicineHoustonUSA

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