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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

ApaI digestion of the 292 bp nested PCR (QPCR) fragment generated from the fragment of 1.12 RT-PCR reactions. Biallelic expression was identifiable by the presence of each of the 292, 227, and 63 bp restriction fragments. First lane shows Fisher's exACTGene 100 bp DNA Ladder, showing the 500 bp–25 bp respective molecular weight size markers.
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fig2: ApaI digestion of the 292 bp nested PCR (QPCR) fragment generated from the fragment of 1.12 RT-PCR reactions. Biallelic expression was identifiable by the presence of each of the 292, 227, and 63 bp restriction fragments. First lane shows Fisher's exACTGene 100 bp DNA Ladder, showing the 500 bp–25 bp respective molecular weight size markers.

Mentions: To analyze imprinting of the IGF-II gene, we selected the samples that were Heterozygous (Het) for the transcribed ApaI polymorphism. A total of 26 Het samples were analyzed to identify allelic expression of the IGF-II gene (Figure 2). Surprisingly, all 26 Het samples (13N + 13M) analyzed were biallelic (BA). Thus, 100% of the Het normal paired samples were BA.


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)

ApaI digestion of the 292 bp nested PCR (QPCR) fragment generated from the fragment of 1.12 RT-PCR reactions. Biallelic expression was identifiable by the presence of each of the 292, 227, and 63 bp restriction fragments. First lane shows Fisher's exACTGene 100 bp DNA Ladder, showing the 500 bp–25 bp respective molecular weight size markers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: ApaI digestion of the 292 bp nested PCR (QPCR) fragment generated from the fragment of 1.12 RT-PCR reactions. Biallelic expression was identifiable by the presence of each of the 292, 227, and 63 bp restriction fragments. First lane shows Fisher's exACTGene 100 bp DNA Ladder, showing the 500 bp–25 bp respective molecular weight size markers.
Mentions: To analyze imprinting of the IGF-II gene, we selected the samples that were Heterozygous (Het) for the transcribed ApaI polymorphism. A total of 26 Het samples were analyzed to identify allelic expression of the IGF-II gene (Figure 2). Surprisingly, all 26 Het samples (13N + 13M) analyzed were biallelic (BA). Thus, 100% of the Het normal paired samples were BA.

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