Down-regulated expression of Notch signaling molecules in human endometrial cancer

Abstract

Notch signaling pathway is a highly conserved developmental pathway, which plays an important role in the regulation of cellular proliferation, differentiation and apoptosis. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. In this study, we investigated the expression of Notch receptors (NOTCH1, NOTCH2, NOTCH3 and NOTCH4), ligands (JAG1, JAG2 and DLL1) and target gene HES1. Fifty paired samples of endometrial cancer and adjacent nontumor endometrial tissue from endometrial cancer patients were analyzed by quantitative PCR. The mRNA levels of all investigated molecules were lower in endometrial cancer compared to adjacent nontumor tissue. The expression of NOTCH1, NOTCH4 and DLL1 in IB stage adenocarcinoma was significantly lower (P < 0.05) than the expression in IA stage adenocarcinoma. Significant correlations were found between mRNA expression levels of Notch target gene HES1 and several Notch signaling molecules: NOTCH1, NOTCH3, DLL1 (P < 0.001) and NOTCH2, JAG2 (P < 0.05). This supports the notion that Notch pathway can function as tumor suppressor in human endometrial cancer.

Blocking NOTCH pathway can enhance the effect of EGFR inhibitor through targeting CD133+ endometrial cancer cells

“…20 As an example, the downregulation of Notch signaling inhibits the growth, migration, and invasiveness of cancer cells and induces cell apoptosis . 21 In the current study, we found that Notch signaling was expressed in both CD133C and CD133-cells. However, compared with CD133-cells, the expression in CD133C cells was higher.…”

Prognostic significance of Notch ligands in patients with non-small cell lung cancer

“…The idea of downregulation of Notch signaling is novel for lung cancer but it is not unexpected in the light of studies performed on other types of cancer, including endometrial cancer. Jonusiene et al (24) investigated the expression of Notch receptors (Notch 1, Notch 2, Notch 3 and Notch 4), ligands (Jag1, Jag2 and Dll1) and target gene Hes1 in endometrial cancer and adjacent non-tumor endometrial tissue from endometrial cancer patients. The mRNA levels of Notch receptors and ligands were reduced in endometrial cancer compared with adjacent non-tumor tissue (24).…”

“…Jonusiene et al (24) investigated the expression of Notch receptors (Notch 1, Notch 2, Notch 3 and Notch 4), ligands (Jag1, Jag2 and Dll1) and target gene Hes1 in endometrial cancer and adjacent non-tumor endometrial tissue from endometrial cancer patients. The mRNA levels of Notch receptors and ligands were reduced in endometrial cancer compared with adjacent non-tumor tissue (24). Furthermore, in contrast to the results of the present study, the expression of Notch1, Notch4 and Dll1 in IB stage adenocarcinoma was significantly reduced compared with the expression of these molecules at the IA stage (16).…”

NOTCH signalinio kelio ir ginekologinių piktybinių navikų sąsaja

“…Mūsų su bendraautoriais atliktų tyrimų, kuriuose nagrinėta gimdos kūno vėžio bei NOTCH signalinio kelio sąsaja, duomenys paskelbti dviejose publikacijose (33,34). Tyrimams naudoti 50 pacienčių mėginiai (tirtas kiekvienos pacientės navikinis ir sveikas endometriumo audinys), gauti operacijos metu pašalinus gimdą.…”