Methylation of the calcium channel regulatory subunit alpha 2 delta-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas. / Palmieri, C.; Rudraraju, B.; Monteverde, M.; Lattanzio, L.; Gojis, O.; Brizio, R.; Garrone, O.; Merlano, M.; Syed, N.; Lo Nigro, C.; Crook, T.
In: British Journal of Cancer, Vol. 107, No. 2, 10.07.2012, p. 375-381.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Methylation of the calcium channel regulatory subunit alpha 2 delta-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas
A1 - Palmieri,C.
A1 - Rudraraju,B.
A1 - Monteverde,M.
A1 - Lattanzio,L.
A1 - Gojis,O.
A1 - Brizio,R.
A1 - Garrone,O.
A1 - Merlano,M.
A1 - Syed,N.
A1 - Lo Nigro,C.
A1 - Crook,T.
AU - Palmieri,C.
AU - Rudraraju,B.
AU - Monteverde,M.
AU - Lattanzio,L.
AU - Gojis,O.
AU - Brizio,R.
AU - Garrone,O.
AU - Merlano,M.
AU - Syed,N.
AU - Lo Nigro,C.
AU - Crook,T.
PY - 2012/7/10
Y1 - 2012/7/10
N2 - <p>BACKGROUND: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer.</p><p>METHODS: We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit alpha 2 delta-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions.</p><p>RESULTS: Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 50 regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-alpha (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system.</p><p>CONCLUSION: Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease. British Journal of Cancer (2012) 107, 375-381. doi:10.1038/bjc.2012.231 www.bjcancer.com Published online 29 May 2012 (c) 2012 Cancer Research UK</p>
AB - <p>BACKGROUND: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer.</p><p>METHODS: We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit alpha 2 delta-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions.</p><p>RESULTS: Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 50 regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-alpha (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system.</p><p>CONCLUSION: Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease. British Journal of Cancer (2012) 107, 375-381. doi:10.1038/bjc.2012.231 www.bjcancer.com Published online 29 May 2012 (c) 2012 Cancer Research UK</p>
U2 - 10.1038/bjc.2012.231
DO - 10.1038/bjc.2012.231
M1 - Article
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 2
VL - 107
SP - 375
EP - 381
ER -