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

Radhakrishnan VK, Hernandez LC, Anderson K, Tan Q, De León M, De León DD - Int J Endocrinol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

(a) Representative bar graph of IGF-II, IGF-I, and Survivin mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (b) Representative bar graph of Insulin-Like Growth Factor-I Receptor (IGF-1R), Insulin-Like Growth Factor-II Receptor (IGF-IIR), Insulin Receptor A (IRA) and Insulin Receptor B (IRB) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (c) Representative bar graph of Estrogen Receptor-α (ESR-α), Human Epidermal Growth factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and Vascular Endothelial Growth Factor Receptor (VEGFR) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate.
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fig6: (a) Representative bar graph of IGF-II, IGF-I, and Survivin mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (b) Representative bar graph of Insulin-Like Growth Factor-I Receptor (IGF-1R), Insulin-Like Growth Factor-II Receptor (IGF-IIR), Insulin Receptor A (IRA) and Insulin Receptor B (IRB) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (c) Representative bar graph of Estrogen Receptor-α (ESR-α), Human Epidermal Growth factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and Vascular Endothelial Growth Factor Receptor (VEGFR) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate.

Mentions: Representative 9 paired samples were selected based on their mRNA quality and were analyzed by quantitative RT-PCR to assess the gene expression of IGF-II, IGF-I, Survivin (Figure 6(a)), IGF-IR, IGF-IIR, Insulin Receptor A (IRA), Insulin Receptor B (IRB) (Figure 6(b)), Estrogen Receptor-α (ESR-α), Human Epidermal Growth Factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and the Vascular Endothelial Growth Factor Receptor (VEGFR) (Figure 6(c)). The 18S rRNA was used to normalize mRNA fold change expression (CFX Bio-Rad Manager, qbase software and GraphPad Prism 5). The data show that normal breast tissues (N) have lower levels of IGF-II, IGF-I, Survivin, and related receptors IGF-IIR, IRA, IRB, ESR-α, ERBB2, PRLR, and VEGFR when compared to the malignant breast tissues. The IGF-IIR, IRA, IRB, and VEGFR are higher in Het when compared to the Hom and Hom SNP.


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

Radhakrishnan VK, Hernandez LC, Anderson K, Tan Q, De León M, De León DD - Int J Endocrinol (2015)

(a) Representative bar graph of IGF-II, IGF-I, and Survivin mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (b) Representative bar graph of Insulin-Like Growth Factor-I Receptor (IGF-1R), Insulin-Like Growth Factor-II Receptor (IGF-IIR), Insulin Receptor A (IRA) and Insulin Receptor B (IRB) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (c) Representative bar graph of Estrogen Receptor-α (ESR-α), Human Epidermal Growth factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and Vascular Endothelial Growth Factor Receptor (VEGFR) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581569&req=5

fig6: (a) Representative bar graph of IGF-II, IGF-I, and Survivin mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (b) Representative bar graph of Insulin-Like Growth Factor-I Receptor (IGF-1R), Insulin-Like Growth Factor-II Receptor (IGF-IIR), Insulin Receptor A (IRA) and Insulin Receptor B (IRB) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate. (c) Representative bar graph of Estrogen Receptor-α (ESR-α), Human Epidermal Growth factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and Vascular Endothelial Growth Factor Receptor (VEGFR) mRNA fold levels from 3 different patient samples ran in three separate qrtPCR assays done in triplicate.
Mentions: Representative 9 paired samples were selected based on their mRNA quality and were analyzed by quantitative RT-PCR to assess the gene expression of IGF-II, IGF-I, Survivin (Figure 6(a)), IGF-IR, IGF-IIR, Insulin Receptor A (IRA), Insulin Receptor B (IRB) (Figure 6(b)), Estrogen Receptor-α (ESR-α), Human Epidermal Growth Factor Receptor 2 (ERBB2/Her2), Prolactin Receptor (PRLR), and the Vascular Endothelial Growth Factor Receptor (VEGFR) (Figure 6(c)). The 18S rRNA was used to normalize mRNA fold change expression (CFX Bio-Rad Manager, qbase software and GraphPad Prism 5). The data show that normal breast tissues (N) have lower levels of IGF-II, IGF-I, Survivin, and related receptors IGF-IIR, IRA, IRB, ESR-α, ERBB2, PRLR, and VEGFR when compared to the malignant breast tissues. The IGF-IIR, IRA, IRB, and VEGFR are higher in Het when compared to the Hom and Hom SNP.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Health Disparities and Molecular Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus