The prolyl 3-hydroxylases P3H2 and P3H3 are novel targets for epigenetic silencing in breast cancer

R. Shah; P. Smith; C. Purdie; P. Quinlan; L. Baker; P. Aman; A. M.  Thompson; T. Crook

doi:10.1038/sj.bjc.6605042

The prolyl 3-hydroxylases P3H2 and P3H3 are novel targets for epigenetic silencing in breast cancer

R. Shah, P. Smith, C. Purdie, P. Quinlan, L. Baker, P. Aman, A. M. Thompson, T. Crook

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

Expression of P3H2 (Leprel1) and P3H3 (Leprel2) but not P3H1 (Leprecan) is down-regulated in breast cancer by aberrant CpG methylation in the 50 regulatory sequences of each gene. Methylation of P3H2 appears specific to breast cancer as no methylation was detected in a range of cell lines from other epithelial cancers or from primary brain tumours or malignant melanoma. Methylation in P3H2, but not P3H3, was strongly associated with oestrogen-receptor-positive breast cancers, whereas methylation in P3H3 was associated with higher tumour grade and Nottingham Prognostic Index. Ectopic expression of P3H2 and P3H3 in cell lines with silencing of the endogenous gene results in suppression of colony growth. This is the first demonstration of epigenetic inactivation of prolyl hydroxylases in human cancer, implying that this gene family represents a novel class of tumour suppressors. The restriction of silencing in P3H2 to breast carcinomas, and its association with oestrogen-receptor-positive cases, suggests that P3H2 may be a breast-cancer-specific tumour suppressor. British Journal of Cancer (2009) 100, 1687-1696. doi: 10.1038/sj.bjc.6605042 www.bjcancer.com (C) 2009 Cancer Research UK

Original language	English
Pages (from-to)	1687-1696
Number of pages	10
Journal	British Journal of Cancer
Volume	100
Issue number	10
DOIs	https://doi.org/10.1038/sj.bjc.6605042
Publication status	Published - 12 May 2009

Keywords

breast cancer
epigenetics
prolyl hydroxylase
MEMBRANE-ASSOCIATED PROTEOGLYCAN
GENE-EXPRESSION
OSTEOGENESIS IMPERFECTA
CELL-LINES
COLLAGEN
FAMILY
HYPERMETHYLATION
SIGNATURE
LEPRECAN
HIF

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.bjc.6605042

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title = "The prolyl 3-hydroxylases P3H2 and P3H3 are novel targets for epigenetic silencing in breast cancer",

abstract = "Expression of P3H2 (Leprel1) and P3H3 (Leprel2) but not P3H1 (Leprecan) is down-regulated in breast cancer by aberrant CpG methylation in the 50 regulatory sequences of each gene. Methylation of P3H2 appears specific to breast cancer as no methylation was detected in a range of cell lines from other epithelial cancers or from primary brain tumours or malignant melanoma. Methylation in P3H2, but not P3H3, was strongly associated with oestrogen-receptor-positive breast cancers, whereas methylation in P3H3 was associated with higher tumour grade and Nottingham Prognostic Index. Ectopic expression of P3H2 and P3H3 in cell lines with silencing of the endogenous gene results in suppression of colony growth. This is the first demonstration of epigenetic inactivation of prolyl hydroxylases in human cancer, implying that this gene family represents a novel class of tumour suppressors. The restriction of silencing in P3H2 to breast carcinomas, and its association with oestrogen-receptor-positive cases, suggests that P3H2 may be a breast-cancer-specific tumour suppressor. British Journal of Cancer (2009) 100, 1687-1696. doi: 10.1038/sj.bjc.6605042 www.bjcancer.com (C) 2009 Cancer Research UK",

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author = "R. Shah and P. Smith and C. Purdie and P. Quinlan and L. Baker and P. Aman and Thompson, {A. M.} and T. Crook",

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doi = "10.1038/sj.bjc.6605042",

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AU - Shah, R.

AU - Smith, P.

AU - Purdie, C.

AU - Quinlan, P.

AU - Baker, L.

AU - Aman, P.

AU - Thompson, A. M.

AU - Crook, T.

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N2 - Expression of P3H2 (Leprel1) and P3H3 (Leprel2) but not P3H1 (Leprecan) is down-regulated in breast cancer by aberrant CpG methylation in the 50 regulatory sequences of each gene. Methylation of P3H2 appears specific to breast cancer as no methylation was detected in a range of cell lines from other epithelial cancers or from primary brain tumours or malignant melanoma. Methylation in P3H2, but not P3H3, was strongly associated with oestrogen-receptor-positive breast cancers, whereas methylation in P3H3 was associated with higher tumour grade and Nottingham Prognostic Index. Ectopic expression of P3H2 and P3H3 in cell lines with silencing of the endogenous gene results in suppression of colony growth. This is the first demonstration of epigenetic inactivation of prolyl hydroxylases in human cancer, implying that this gene family represents a novel class of tumour suppressors. The restriction of silencing in P3H2 to breast carcinomas, and its association with oestrogen-receptor-positive cases, suggests that P3H2 may be a breast-cancer-specific tumour suppressor. British Journal of Cancer (2009) 100, 1687-1696. doi: 10.1038/sj.bjc.6605042 www.bjcancer.com (C) 2009 Cancer Research UK

AB - Expression of P3H2 (Leprel1) and P3H3 (Leprel2) but not P3H1 (Leprecan) is down-regulated in breast cancer by aberrant CpG methylation in the 50 regulatory sequences of each gene. Methylation of P3H2 appears specific to breast cancer as no methylation was detected in a range of cell lines from other epithelial cancers or from primary brain tumours or malignant melanoma. Methylation in P3H2, but not P3H3, was strongly associated with oestrogen-receptor-positive breast cancers, whereas methylation in P3H3 was associated with higher tumour grade and Nottingham Prognostic Index. Ectopic expression of P3H2 and P3H3 in cell lines with silencing of the endogenous gene results in suppression of colony growth. This is the first demonstration of epigenetic inactivation of prolyl hydroxylases in human cancer, implying that this gene family represents a novel class of tumour suppressors. The restriction of silencing in P3H2 to breast carcinomas, and its association with oestrogen-receptor-positive cases, suggests that P3H2 may be a breast-cancer-specific tumour suppressor. British Journal of Cancer (2009) 100, 1687-1696. doi: 10.1038/sj.bjc.6605042 www.bjcancer.com (C) 2009 Cancer Research UK

KW - breast cancer

KW - epigenetics

KW - prolyl hydroxylase

KW - MEMBRANE-ASSOCIATED PROTEOGLYCAN

KW - GENE-EXPRESSION

KW - OSTEOGENESIS IMPERFECTA

KW - CELL-LINES

KW - COLLAGEN

KW - FAMILY

KW - HYPERMETHYLATION

KW - SIGNATURE

KW - LEPRECAN

KW - HIF

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DO - 10.1038/sj.bjc.6605042

M3 - Article

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SN - 0007-0920

VL - 100

SP - 1687

EP - 1696

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 10

ER -

The prolyl 3-hydroxylases P3H2 and P3H3 are novel targets for epigenetic silencing in breast cancer

Abstract

Keywords

UN SDGs

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