Transcriptional analysis of estrogen receptor alpha variant mRNAs in colorectal cancers and their matched normal colorectal tissues

Estrogen is involved in suppression of colorectal cancer development and exerts its function via estrogen receptors a, (3 and their splicing variants. Whether the recently indentified ER-alpha splicing variants, ER-alpha 36 and ER-alpha 46, play a role in colorectal cancer development is unknown. In this study, we quantified the mRNA copy numbers of wild type ER-alpha (ER-alpha 66), ER-alpha 46 and ER-alpha 36 in 35 colorectal cancers and their matched normal colorectal tissues by quantitative real-time PCR assay, and correlated their mRNA levels with the clinicopathological properties of the tumors. We found that ER-alpha 66, ER-alpha 46 and ER-alpha 36 mRNAs were coexpressed in all colorectal cancers and their matched normal tissues. The decreased mRNA levels of ER-alpha 36 and ER-alpha 46 whereas no difference of ER-alpha 66 mRNA was observed in colorectal cancers compared to their matched normal tissues. Moreover, change in the expression of ER-alpha 36 mRNA level was correlated with Dukes' stage of the tumor and the lymph node metastasis. ER-alpha 36 mRNA was decreased significantly in Dukes' C+D compared to Dukes' A+B stage tumors (P=0.017), and the expression of ER-alpha 36 mRNA in N-1/N-2 was lower than that in No lymph node metastasis (P=0.049). So ER-alpha 36 and ER-alpha 46 might be implicated in the development and progression of colorectal cancers. (C) 2008 Elsevier Ltd. All rights reserved.