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Endocrinology |
Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida 32610
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
and ERß, mediate genomic
effects in target cells. The aim of this study was to determine the
relative mRNA expression levels for ER subtypes and ERß isoforms in
colon tumors, normal colonic mucosa, and colon cancer cell lines. ER
and ERß 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 ERß levels were further studied in Caco-2 cells using Northern
and Western analyses. ERß mRNA steady-state levels (relative to
glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly
decreased in colon tumors compared with normal mucosa in female
patients. ERß1 and ERß2 isoform mRNA levels were significantly
decreased in tumors from female patients, and ERß1 mRNA levels were
also significantly lower in tumors from female patients compared with
tumors from males. ER mRNA levels were much lower than ERß levels
and were similar between normal mucosa and tumor samples in both
genders. ERß mRNA was detected in Caco-2, T84, and SW1116 cell lines
and all lines were essentially negative for ER mRNA. Caco-2 cells
coexpressed ERß1, ERß2, and ERß5 mRNA, though a single protein
transcript was observed. ERß protein was detected in normal colonic
superficial epithelium, vascular smooth muscle and endothelium, and
enteric neurons by immunohistochemistry. These data show that ERß is
the predominant ER subtype in the human colon and that decreased levels
of ERß1 and ERß2 mRNA are associated with colonic tumorigenesis in
females. This information suggests that activation of ERß-mediated
processes in the superficial colonic epithelium may have a role in the
preventive effects observed for female gender and ERT usage.
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