Reintroduction of IGF‑1R into miR‑320a‑overexpressed cells antagonized the impact of miR‑320a on its downstream protein, which demonstrated that the tumor suppressive role of miR‑320a in endometrial carcinoma is exerted by the signal pathway mediated by IGF‑1R.
We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer.
In the present study, polymorphisms of the IGF-1 promoter may have been introduced during the genesis of EC and contributed to it by leading to aberrant expression of IGF-1.
To test the hypothesis that insulin signalling plays a key role in the development of EC in women with PCOS by measuring and comparing the expression of three key genes involved in the insulin signalling pathway (IGF1, PTEN and IGFBP1) in endometrial tissue obtained from three groups of women; PCOS without EC, women with EC without PCOS and non-PCOS women without EC (controls).
In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.
This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer.
Results showed that RNAi mediated down-regulation of IGF-1R expression in endometrial carcinoma significantly induced apoptosis, reduced downstream protein phosphorylation and decreased tumorigenicity in vivo accompanied with lower proliferation index in tumor tissue, Which implied the therapeutic potential of RNAi in the treatment of endometrial carcinoma by targeting IGF-1R and IGF-1R may be a potential therapeutic target for human endometrial carcinoma.
Lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma.
Autocrine stimulation of IGF1 in estrogen-induced growth of endometrial carcinoma cells: involvement of the mitogen-activated protein kinase pathway followed by up-regulation of cyclin D1 and cyclin E.
Furthermore, endometrial tissue-pair analysis revealed a significant positive correlation between EGF and IGF-1 (P=0.010), supporting the hypothesis of a cross-talk between IGF- and EGF-mediated signaling pathways in endometrial cancer.
It has been shown that: (i) high serum concentrations of IGF-1 and IGF-2 are associated with an increased risk of breast, prostate, colorectal and lung cancers; and (ii) IGF-R1 is commonly disturbed in many tumours (like gastric, lung, endometrial cancer) leading to a phenotype of anchorage-independent tumour growth.
Further work is needed to establish if IGF-1 plays a role in a subset of endometrial cancers and if isoforms of VEGF play a role in endometrial cancer.
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.
Our results demonstrate a reduced expression of IGF-I mRNA in endometrial carcinomas compared with non-neoplastic tissues, despite equivalent immunohistochemical expression of IGF-I and IGF-I receptor.
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 with adenomatous hyperplasia (type I EC).