Selective loss of estrogen receptor beta in malignant human colon

Epidemiological data suggest a protective effect for estrogen replacement therapy on colon cancer. The estrogen receptor (ER) is required for the action of estrogen. The ER-beta isoform is functionally similar to ER-alpha but has a distinct pattern of expression and transcriptional response to selective estrogen response modulators. Our goal was to investigate the presence of ER-alpha and ER-beta in normal and malignant colon tissue. Human colon cancer tissue and adjacent normal colon tissue were harvested from five male and six female patients undergoing segmental colon resection for colon cancer. Western blot analysis revealed very low levels of ER-alpha protein in tumor and normal colon tissue. In both male and female patients, malignant colon tissue showed a selective loss of ER-beta protein expression when compared to normal colon tissue in the same patient. Semiquantitative reverse transcription-PCR revealed no difference in ER-beta mRNA levels between normal and malignant colon tissue. Malignant transformation of the colon is associated with a marked diminution of ER-beta protein expression, possibly through a posttranscriptional mechanism.