Id1 overexpression is independent of repression and epigenetic silencing of tumor suppressor genes in melanoma

Abstract

The full molecular consequences of oncogene activation during tumorigenesis are not well understood, but several studies have recently linked oncogene activation to epigenetic silencing of specific genes.1,2 Transcriptional repressor Id1 is overexpressed in many malignancies including melanoma, and Id1 targets include tumor suppressor genes TSP1, CDKN2A (p16) and CDKN1A (p21), which are frequently epigenetically silenced in cancer. We confirmed that both TSP1 and CDKN2A have abnormal promoter region DNa methylation in primary melanoma, but the mechanism by which this silencing occurs remains unknown. Here we explore the effects of stable lentiviral Id1 overexpression on the expression of these Id1 target genes in human melanoma cell lines. Overexpressed Id1 was functional and bound transcriptional activator E2A, but did not sequester E2A from gene promoters and repress gene expression. Therefore, these Id1 target genes were resistant to Id1-mediated gene silencing. Our results suggest that Id1 activation may need to occur at discrete stages in cooperation with additional gene dysregulation to repress and induce epigenetic silencing of tumor suppressor genes during melanoma progression.

The Aberrant Promoter Hypermethylation Pattern of the Anti - Angiogenic Tsp1 Gene in Epithelial Ovarian Carcinoma: An Indian Study

“…Megan. A. Healey 11 reported a 13% and 20% methylation of TSP1 in their study on primary melanoma and melanoma cell lines respectively. A 10 and 7% methylation was observed in esophageal squamous cell carcinoma and pancreatic adenocarcinoma respectively.…”

“…Primers were designed to amplify the DNA template irrespective of the methylation status as previously mentioned. 11 The PCR product from the first step was diluted 10-folds and used as template for the second step where primers were designed to specifically amplify the methylated and the unmethylated regions of the TSP1 promoter. CpG Methylated HeLa Genomic DNA (New England Biolabs, USA) was used as a positive control for methylated allele and DNA obtained from the of normal ovary samples served as negative control.…”

Suppression of ID1 expression in colon cancer cells increases sensitivity to 5-fluorouracil

“…These transitional forms are called hybrid epithelial/mesenchymal phenotype (Jolly et al, 2015). It was also noted that stable lentiviral ID1 overexpression producing functional protein in melanoma cells failed to affect transcription/translation of the ID1 target genes suggesting that ID1 expression alone is insufficient to determine cell fate (Healey et al, 2010). Thus, it may be assumed that specific response triggered by ID1 depends on molecular context in the cancer cell or its environment.…”

<p>Id-1 Promotes Reendothelialization In The Early Phase After Vascular Injury Through Activation Of NFkB/survivin Signaling Pathway</p>

“…Recent studies have revealed that Id1 can inhibit cell apoptosis and promote angiogenesis by activating nuclear factor kappa B (NF-kappa B)/survivin-related signaling pathway, and ultimately promote the proliferation of a variety of cancer cells 15–19. NF-kappa B can regulate the expression of survivin, which is a new member of the inhibitor of apoptosis protein (IAP) family.…”