Limits...
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

Representative standard sequencing alignment for IGF-II Exon 9 region chromosome 11: 2153626–2153683 (58 bp). The sequenced samples show that the Heterozygous (Het) and the Homozygous with SNP tissues have the (C) cytosine and the Homozygous samples have the (T) Thymidine in reference to the USCS genome Feb. 2009 (GRCh37/hg19) released version as reference gene.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4581569&req=5

fig3: Representative standard sequencing alignment for IGF-II Exon 9 region chromosome 11: 2153626–2153683 (58 bp). The sequenced samples show that the Heterozygous (Het) and the Homozygous with SNP tissues have the (C) cytosine and the Homozygous samples have the (T) Thymidine in reference to the USCS genome Feb. 2009 (GRCh37/hg19) released version as reference gene.

Mentions: The gDNA PCR products of the TNBC samples were sequenced to show the rs680 SNP with reference USCS genome browser Feb. 2009 (GRCh37/hg19) released version for IGF-II Exon 9. The sequenced samples show that the BA and the MAS tissues have the (C) cytosine and the MA samples have the (T) Thymidine in reference to the human genome web browser (http://genome.ucsc.edu/). This sequence verified the IGF-II allelic pattern and confirmed the gDNA ApaI restriction enzyme digestion pattern as shown in Figures 1 and 3. The samples were sequenced using the reverse primer 5′-GGTCGTGCCAATTACATTTCA-3′ to identify the allelic pattern for IGF-II at Exon 9 and aligned by EMBI Clustal W software.


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)

Representative standard sequencing alignment for IGF-II Exon 9 region chromosome 11: 2153626–2153683 (58 bp). The sequenced samples show that the Heterozygous (Het) and the Homozygous with SNP tissues have the (C) cytosine and the Homozygous samples have the (T) Thymidine in reference to the USCS genome Feb. 2009 (GRCh37/hg19) released version as reference gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Representative standard sequencing alignment for IGF-II Exon 9 region chromosome 11: 2153626–2153683 (58 bp). The sequenced samples show that the Heterozygous (Het) and the Homozygous with SNP tissues have the (C) cytosine and the Homozygous samples have the (T) Thymidine in reference to the USCS genome Feb. 2009 (GRCh37/hg19) released version as reference gene.
Mentions: The gDNA PCR products of the TNBC samples were sequenced to show the rs680 SNP with reference USCS genome browser Feb. 2009 (GRCh37/hg19) released version for IGF-II Exon 9. The sequenced samples show that the BA and the MAS tissues have the (C) cytosine and the MA samples have the (T) Thymidine in reference to the human genome web browser (http://genome.ucsc.edu/). This sequence verified the IGF-II allelic pattern and confirmed the gDNA ApaI restriction enzyme digestion pattern as shown in Figures 1 and 3. The samples were sequenced using the reverse primer 5′-GGTCGTGCCAATTACATTTCA-3′ to identify the allelic pattern for IGF-II at Exon 9 and aligned by EMBI Clustal W software.

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