{'fraction_non_alphanumeric': 0.01965163019205002, 'fraction_numerical': 0.009379187137114784, 'mean_word_length': 5.1707988980716255, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Expression of Estrogen Receptor ( ER ) Subtypes and ER b Isoforms in Colon Cancer 1

Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ER a and ERb, mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ER b isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ERa and ERb isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ERb levels were further studied in Caco-2 cells using Northern and Western analyses. ERb mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ERb1 and ERb2 isoform mRNA levels were significantly decreased in tumors from female patients, and ERb1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ERa mRNA levels were much lower than ERb levels and were similar between normal mucosa and tumor samples in both genders. ER b mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ERa mRNA. Caco-2 cells coexpressed ER b1, ERb2, and ERb5 mRNA, though a single protein transcript was observed. ERb protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ERb is the predominant ER subtype in the human colon and that decreased levels of ER b1 and ERb2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ERb-mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage.