3q21.1 HGNC:1514 ENSG00000036828 Entrez:846
Thursday 17 March 2011
Ca(2+) is a chemopreventive agent for colon cancer.
- Ion transport systems are often altered in human cancer.
- CpG islands are densely methylated in cancer cell lines with reduced CASR mRNA expression.
- Treatment with a demethylating agent, 5-aza-2’-deoxycytidine, and/or a histone deacetylase inhibitor, trichostatin A, restores CASR expression in the cancer cell lines.
- Disruption of CASR expression in CASR-unmethylated HCT-8 cells blocsd the enhancing effect of Ca(2+) on the cytotoxic response to 5-fluorouracil.
- CASR expression is observed in normal colonic epithelial cells and was retained in most adenoma tissues.
- CASR mRNA and protein expression is significantly downregulated in cancer tissues.
- There is an inverse relationship between CASR expression and degree of differentiation.
- Immunohistochemical CASR staining is reduced more predominantly in less-differentiated cancer tissues and/or in cancer cells at the invasive front, where nuclear/cytoplasmic β-catenin was often localized.
- CASR methylation is detected in 69% of colorectal cancer tissues and 90% of lymph node metastatic tissues and was significantly correlated with reduced CASR expression.
- CASR methylation is also detected in 32% of advanced adenoma tissues but was detected in only 9% of adenoma tissues and was not detected in hyperplastic polyp tissues.
- CASR methylation seems to occur at an early stage and progress in colorectal carcinogenesis.
- Epigenetic inactivation of CASR could have an important role in colorectal carcinogenesis.
Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma. Witteveen JE, Hamdy NA, Dekkers OM, Kievit J, van Wezel T, Teh BT, Romijn JA, Morreau H. Mod Pathol. 2011 May;24(5):688-97. PMID: 21240254
Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis. Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, Kato N, Sukawa Y, Sanchez JV, Suzuki H, Sasaki S, Imai K, Shinomura Y. Mod Pathol. 2011 Feb 11. PMID: 21317879 (Free)