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Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer

ABSTRACT: The insulin-like growth factor-I (IGF-IR) and androgen (AR) receptors are important players in prostate cancer biology. Functional interactions between the IGF-I and androgen signaling pathways seem to have crucial roles in the progression of prostate cancer from early (benign) to advanced (metastatic) stages. DNA methylation is a major epigenetic alteration affecting gene expression. Hypermethylation of tumor suppressor promoters is a frequent event in human cancer, leading to inactivation and repression of specific genes. The aim of the present study was to identify the entire set of methylated genes (“methylome”) in a cellular model that replicates prostate cancer progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34042 | GEO | 2012/12/12

SECONDARY ACCESSION(S): PRJNA148087

REPOSITORIES: GEO

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Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer

Project description:The insulin-like growth factor-I (IGF-IR) and androgen (AR) receptors are important players in prostate cancer biology. Functional interactions between the IGF-I and androgen signaling pathways seem to have crucial roles in the progression of prostate cancer from early (benign) to advanced (metastatic) stages. DNA methylation is a major epigenetic alteration affecting gene expression. Hypermethylation of tumor suppressor promoters is a frequent event in human cancer, leading to inactivation and repression of specific genes. The aim of the present study was to identify the entire set of methylated genes (M-bM-^@M-^\methylomeM-bM-^@M-^]) in a cellular model that replicates prostate cancer progression. The methylation profiles of the P69 (early stage, benign) and M12 (advanced stage, metastatic) prostate cancer cell lines were established by treating cells with the demethylating agent 5-Aza-2M-bM-^@M-^Y-deoxycytidine (5-Aza) followed by DNA microarray analysis. Comparative genome-wide methylation analyses of 5-Aza-treated versus untreated cells identified 297 genes overexpressed in P69 and 191 genes overexpressed in M12 cells. One hundred and two genes were upregulated in both benign and metastatic cell lines. In addition, our analyses identified the PITX2 gene as a master regulator upstream of the AR and IGF-IR genes.

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