Discordant expression of insulin-like growth factors and their receptor messenger ribonucleic acids in endometrial carcinomas relative to normal endometrium

The inappropriate expressions of insulin-like growth factors (IGF-I and II) and IGF-I receptor (IGF-IR) are implicated in the malignant growth of many cancers. To determine changes, if any, in the levels of expression of IGFs and IGF receptor genes in neoplastic endometrium, relative to normal endom etrium, the mRNA levels of IGF-I and II and of IGF-IR and IIR were measured in samples of endometrial carcinomas (EC) and normal endometrium, through all phases of the menstrual cycle, by semiquantitative reverse transcriptio n-polymerase chain reaction (RT-PCR) assays. In normal endometrium, the mRN A levels of IGF-I were elevated in the proliferative and early secretory ph ases. The IGF-II mRNAs were relatively high in the proliferative phase, but unaltered through early and late secretory phases. Significantly elevated levels of IGF-II transcripts were observed during the menstrual phase, sugg esting a possible role of IGF-II in endometrial regeneration. A positive co rrelation between the levels of IGF-I and IGF-IR mRNAs, apparent in the sam ples of normal endometrium, was not observed in endometrial carcinomas. The IGF-IR and IIR mRNA levels were elevated in endometrial carcinoma samples. On the other hand, the IGF-I and II mRNA levels were conspicuously low in many carcinoma samples, which were not associated with hyperplasia (type II EC), but relatively elevated in two other carcinoma samples, associated wi th adenomatous hyperplasia (type I EC). These results albeit with few sampl es suggest the possibility that the overexpressed receptor, IGF-IR, could b e activated differently in two types of endometrial carcinomas, namely liga nd-dependently in type I ECs and ligand-independently in type II ECs. (C) 1 999 Published by Elsevier Science Ireland Ltd. All rights reserved.