The 40bp Indel Polymorphism rs150550023 in the MDM2 Promoter is Associated with Intriguing Shifts in Gene Expression in the p53-MDM2 Regulatory Hub

Cancers
Heidi MiedlMartin Schreiber

Abstract

Most low-penetrance genetic risk factors for cancer are located in noncoding regions, presumably altering the regulation of neighboring genes. The poorly characterized Indel polymorphism rs150550023 (rs3730485; del1518) in the promoter of MDM2 (human homolog of mouse double minute 2) is a biologically plausible candidate genetic risk factor, which might influence the expression of MDM2, a key negative regulator of the central tumor suppressor p53. Here, we genotyped rs150550023 in a Central European hospital-based case-control study of 407 breast cancer patients and 254 female controls. mRNA levels of MDM2, p53, and the p53 target genes p21, BAX, and PERP were quantified with qRT-PCR, and p53 protein was assessed with immune histochemistry in ≈100 primary breast tumors with ascertained rs150550023 genotype. We found no evidence for an association of rs150550023 with the risk, age at onset, or prognosis of breast cancer. A possible synergism was observed with SNP309 in promoter P2 of MDM2. Mean mRNA levels of MDM2, p53, p21, and BAX were ≈1.5-3 fold elevated in TP53 wildtype tumors with the minor homozygous Del/Del genotype. However, systematic shifts in p53 protein levels or mutation rates were not observed, suggesting that the...Continue Reading

References

Jan 1, 1988·Cancer Treatment and Research·M R Stampfer, J C Bartley
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M TrimarchiJ A Lees
Apr 12, 2001·Journal of Clinical Epidemiology·R Bender, S Lange
Mar 6, 2003·Human Mutation·Anne-Lise Børresen-Dale
Sep 10, 2005·International Journal of Cancer. Journal International Du Cancer·Zhibin HuHongbing Shen
May 27, 2006·Endocrine-related Cancer·Marc LacroixGuy Leclercq
Jul 20, 2006·Cancer Research·Shulin Wang, Wafik S El-Deiry
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marta Sanchez-CarbayoCarlos Cordon-Cardo
Dec 19, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Zhibin HuHongbing Shen
Mar 19, 2008·Genes & Development·Kristen JepsenMichael G Rosenfeld
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Meilin WangZhengdong Zhang
Jun 11, 2009·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Shan KangYan Li
Jul 11, 2009·Breast Cancer Research and Treatment·Konstantinos P Economopoulos, Theodoros N Sergentanis
Nov 6, 2009·The Journal of Biological Chemistry·Seth FrietzePeggy J Farnham
Dec 19, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Byeong-Seon JeongArnold J Levine
Mar 23, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Anna VilborgKlas G Wiman
Jan 13, 2011·Breast Cancer Research : BCR·Angelika BrekmanJill Bargonetti
Jul 5, 2011·Molecular Biology Reports·Erjiang ZhaoWeiquan Lu
Nov 26, 2011·Bioscience Reports·Gina M Bernardo, Ruth A Keri
Apr 21, 2012·Breast Cancer Research : BCR·Rachel L DusekLaura D Attardi
Dec 19, 2012·Human Genomics·Marie-Eve LalondeDaniel Sinnett
Jan 11, 2013·Nature Reviews. Cancer·Mark WadeGeoffrey M Wahl
Jul 3, 2013·Vitamins and Hormones·Rong LiuCeshi Chen
Jul 28, 2013·International Journal of Molecular Sciences·Eva TaubenschußMartin Schreiber
Apr 18, 2014·Nature Reviews. Cancer·Kathryn T BiegingLaura D Attardi
Aug 17, 2014·Genes & Development·Vinod Pant, Guillermina Lozano
Dec 17, 2014·The Journal of Obstetrics and Gynaecology Research·Saeedeh SalimiMinoo Yaghmaei

❮ Previous
Next ❯

Methods Mentioned

BETA
Genotyping
PCR
electrophoresis
transfection
reverse transcription PCR

Software Mentioned

BP
JASPAR
R
CIS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

International Journal of Cancer. Journal International Du Cancer
J L KoH Lee
Acta Biochimica Et Biophysica Sinica
Yuhan ZhaoWenwei Hu
Cellular and Molecular Life Sciences : CMLS
D A FreedmanArnold J Levine
© 2021 Meta ULC. All rights reserved