Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients

African American women suffer higher incidence and mortality of triple negative breast cancer (TNBC) than Caucasian women. TNBC is very aggressive, causing the worst clinical outcome. We previously demonstrated that tumors from these patients express high IGF-II and exhibit high activation of the IG...

Full description

Saved in:
Bibliographic Details
Main Authors: Vinodh Kumar Radhakrishnan, Lorraine Christine Hernandez, Kendra Anderson, Qianwei Tan, Marino De León, Daisy D. De León
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2015/401851
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832562598062587904
author Vinodh Kumar Radhakrishnan
Lorraine Christine Hernandez
Kendra Anderson
Qianwei Tan
Marino De León
Daisy D. De León
author_facet Vinodh Kumar Radhakrishnan
Lorraine Christine Hernandez
Kendra Anderson
Qianwei Tan
Marino De León
Daisy D. De León
author_sort Vinodh Kumar Radhakrishnan
collection DOAJ
description African American women suffer higher incidence and mortality of triple negative breast cancer (TNBC) than Caucasian women. TNBC is very aggressive, causing the worst clinical outcome. We previously demonstrated that tumors from these patients express high IGF-II and exhibit high activation of the IGF signaling pathways. IGF-II gene expression is imprinted (monoallelic), promotes tumor progression, and metastasis and regulates Survivin, a TNBC prognostic marker. Since BC mortality has increased among young Vietnamese women, we analyzed 48 (paired) TNBC samples from Vietnamese patients to assess IGF-II expression. We analyzed all samples by qrtPCR for identification of IGF-II heterozygosity and to determine allelic expression of the IGF-II gene. We also analyzed the tissues for proIGF-II and Survivin by RT-PCR and Western blotting. A total of 28 samples displayed IGF-II heterozygosity of which 78% were biallelic. Tumors with biallelic IGF-II gene expression exhibited the highest levels of proIGF-II and Survivin. Although 100% of these tissues corresponding normal samples were biallelic, they expressed significantly lower levels of or no proIGF-II and Survivin. Thus, IGF-II biallelic gene expression is differentially regulated in normal versus tumor tissues. We propose that intratumoral proIGF-II is dependent on the IGF-II gene imprinting status and it will promote a more aggressive TNBC.
format Article
id doaj-art-442e0f1c2c52408d90e7a983f7cf60aa
institution Kabale University
issn 1687-8337
1687-8345
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series International Journal of Endocrinology
spelling doaj-art-442e0f1c2c52408d90e7a983f7cf60aa2025-02-03T01:22:11ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/401851401851Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese PatientsVinodh Kumar Radhakrishnan0Lorraine Christine Hernandez1Kendra Anderson2Qianwei Tan3Marino De León4Daisy D. De León5Center for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USACenter for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USACenter for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USACenter for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USACenter for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USACenter for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USAAfrican American women suffer higher incidence and mortality of triple negative breast cancer (TNBC) than Caucasian women. TNBC is very aggressive, causing the worst clinical outcome. We previously demonstrated that tumors from these patients express high IGF-II and exhibit high activation of the IGF signaling pathways. IGF-II gene expression is imprinted (monoallelic), promotes tumor progression, and metastasis and regulates Survivin, a TNBC prognostic marker. Since BC mortality has increased among young Vietnamese women, we analyzed 48 (paired) TNBC samples from Vietnamese patients to assess IGF-II expression. We analyzed all samples by qrtPCR for identification of IGF-II heterozygosity and to determine allelic expression of the IGF-II gene. We also analyzed the tissues for proIGF-II and Survivin by RT-PCR and Western blotting. A total of 28 samples displayed IGF-II heterozygosity of which 78% were biallelic. Tumors with biallelic IGF-II gene expression exhibited the highest levels of proIGF-II and Survivin. Although 100% of these tissues corresponding normal samples were biallelic, they expressed significantly lower levels of or no proIGF-II and Survivin. Thus, IGF-II biallelic gene expression is differentially regulated in normal versus tumor tissues. We propose that intratumoral proIGF-II is dependent on the IGF-II gene imprinting status and it will promote a more aggressive TNBC.http://dx.doi.org/10.1155/2015/401851
spellingShingle Vinodh Kumar Radhakrishnan
Lorraine Christine Hernandez
Kendra Anderson
Qianwei Tan
Marino De León
Daisy D. De León
Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
International Journal of Endocrinology
title Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
title_full Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
title_fullStr Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
title_full_unstemmed Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
title_short Expression of Intratumoral IGF-II Is Regulated by the Gene Imprinting Status in Triple Negative Breast Cancer from Vietnamese Patients
title_sort expression of intratumoral igf ii is regulated by the gene imprinting status in triple negative breast cancer from vietnamese patients
url http://dx.doi.org/10.1155/2015/401851
work_keys_str_mv AT vinodhkumarradhakrishnan expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients
AT lorrainechristinehernandez expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients
AT kendraanderson expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients
AT qianweitan expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients
AT marinodeleon expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients
AT daisyddeleon expressionofintratumoraligfiiisregulatedbythegeneimprintingstatusintriplenegativebreastcancerfromvietnamesepatients