Effects of estrogen on messenger ribonucleic acid expression patterns of extracellular matrix proteases in the primate colon.
OBJECTIVE
Recent studies suggest that hormone replacement therapy in postmenopausal women can decrease colon cancer risk. To better understand the molecular effects of estrogen on the colon, we examined the effects of estrogen replacement on gene expression of proteases associated with extracellular matrix degradation in rhesus monkey colon tissue.


METHODS
Rhesus monkeys were oophorectomized and one-half were implanted with estradiol capsules. After five months, colon tissue was harvested, and messenger ribonucleic acid was extracted and converted to cDNA. The cDNA was hybridized with a DNA array spotted with cDNA corresponding to genes involved in extracellular matrix remodeling. Selected genes exhibiting significant differential expression were validated using reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction analysis.


RESULTS
Of 96 genes assessed, nearly 18 percent showed a twofold or greater change in expression; however, signals from approximately 65 percent of genes assayed were below detection levels. A distinct pattern of decreased gene expression was observed in colon tissue of animals with estrogen implants compared with females without estrogen replacement. Reverse transcriptase-polymerase chain reaction confirmed decreased expression in estrogen-replaced vs. hormone-deprived tissues of proteases cathepsin-D and caspase-8. Real-time polymerase chain reaction data confirmed the suppression of proteases A disintegrin and mettaloproteinase with thrombospondin motifs, type 1 and matrix metalloproteinase-2 with estrogen replacement in colon tissue.


CONCLUSIONS
This is the first investigation of the specific effects of estrogen in normal primate colon. Estrogen replacement suppressed expression of several proteases linked to tumor growth and metastasis. This study provides the groundwork for targeted future studies to further characterize the role of estrogen in colon tissue.
Mills
Steven
S
Department of Surgery, Oregon Health & Science University, Portland, Oregon 97239, USA. millsst@ohsu.edu
Young
Kelly A
KA
Whiteford
Mark H
MH
D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000187:drug effects; D003106:Colon / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010450:Endopeptidases / Q000032:analysis* / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006728:Hormones / Q000494:pharmacology*; D008253:Macaca mulatta; D023421:Models, Animal; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics
D015815:Cell Adhesion Molecules; D006728:Hormones; D012333:RNA, Messenger; D004958:Estradiol; D010450:Endopeptidases