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...
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Wiley
2015-01-01
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Series: | International Journal of Endocrinology |
Online Access: | http://dx.doi.org/10.1155/2015/401851 |
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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. |
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institution | Kabale University |
issn | 1687-8337 1687-8345 |
language | English |
publishDate | 2015-01-01 |
publisher | Wiley |
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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 |
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