Effect of tamoxifen treatment on the endometrial expression of human insulin-like growth factors and their receptor mRNAs.
The effect of tamoxifen (Tam) treatment on the endometrial expression of IGF-I and II/IGF-IR and IIR mRNAs was assessed by measuring the levels of expression of these mRNAs in the endometrial samples of Tam-treated postmenopausal breast cancer patients by RT-PCR assays. The levels of these mRNAs were compared with those in normal endometrium and in Type I and Type II endometrial carcinomas (EC). The promoter-specific transcript profiles of IGF-I and II were also elucidated. The levels of IGF/IGF-R mRNAs in the endometrium from Tam-treated patients were found to be comparable with the high levels of these mRNAs observed in the proliferative and early secretory phase endometrium and in the samples of Type I EC. These results indicate that Tam acts as an estrogen agonist in inducing the endometrial expression of these genes. Tam stimulated transcription from the multiple promoters of IGF-I and II, with the exception of IGF-II P2 promoter, in which case the transcription across exon 4 appeared to be inhibited. The profiles of IGF-I and II transcripts of endometrium from Tam-treated patients were similar to Type I EC but differed considerably from those of Type II EC. These results suggest that the Tam-associated ECs are likely to be similar to type I EC and will therefore have a more favorable prognosis.
Department of Obstetrics and Gynecology, St. Michael's Hospital, 30 Bond Street, Room 7-074, Ont. M5B 1W8, Toronto, Canada.
R N
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Roy
A H
AH
Gerulath
A
A
Cecutti
B R
BR
Bhavnani
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D017451:Receptors, Somatomedin / Q000235:genetics*; D013002:Somatomedins / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017527:Receptor, IGF Type 2; D017451:Receptors, Somatomedin; D013002:Somatomedins; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1