Evaluation of expression of PTEN gene may turn out to be a very useful tool aimed at qualifying patients for different therapies of endometrial cancer and at searching of new diagnostic and therapeutic methods of this cancer independently on its receptor status nor maturity grade of cancer.
We genotyped a total of 48 potentially functional SNPs in 11 key genes (AKT1, AKT2, AKT3, BRAF, FRAP1, KRAS, PDPK1, PIK3CA, PIK3CB, PIK3R1, and PTEN) with the Sequenom genotyping platform in 115 endometrial cancer patients and 230 cancer-free women to evaluate their associations with risk, survival, and recurrence of endometrial cancer.
In this study, it appears that tamoxifen-associated endometrial cancers are not significantly different from sporadic endometrial cancer with regards to PTEN IHC expression, although there is a trend towards retained PTEN expression.
Although these data do not preclude the possibility of an increased risk of endometrial cancer in association with the Cowden syndrome, they indicate that germline PTEN mutations do not account for a significant proportion of genetic attributable risk for endometrial carcinoma.
TTF-1 and PTEN can be used as molecular markers for the early diagnosis of endometrial cancer, which are closely related to clinical features and may affect tumor progression by regulating the proliferation activity of tumor cells.
Proliferation, transwell and apoptosis assay suggested that MDH2 enhanced the proliferation, migration and invasion but inhibited the apoptosis of endometrial cancer cell line through suppressing PTEN.
Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay.
We investigated the effects of ABTL0812 on proliferation, cell death and modulation of intracellular signaling pathways in a wide panel of endometrioid and non-endometrioid cell lines, an inducible PTEN knock-out murine model, and two patient-derived xenograft murine models of EC.
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).
Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced.
Sequencing analysis of entire coding region of PTEN/MMAC1 gene revealed mutations in three of six endometrial cancer cell lines (50%) and 17 of 44 endometrial cancer tissues (39%).
For example, PTEN/AKT pathway and its downstream targets and the mTOR (mammalian target of rapamycin) pathway have been shown to play an important role in endometrial cancer pathogenesis.
In this study, we analyzed mutations in 11 cancer-related genes with mononucleotide repeats susceptible to MSI in a coding region [hMSH3 (A8), hMSH6 (C8), TGF-beta RII (A10), MBD4 (A10), BAX (G8), PTEN (A6 in exon 7), HDAC2 (A9), EPHB2 (A9), Caspase-5 (A10), TCF-4 (A9) and Axin2 (G7)] in 22 patients with MSI-H sporadic endometrial cancer.
Enhanced cell growth inhibition following PTEN nonviral gene transfer using polyethylenimine and photochemical internalization in endometrial cancer cells.
Adenovirus-mediated gene transfer was carried out using Ishikawa 3 H 12 and RL95-2, the endometrial cancer cell lines with completely inactivated PTEN, together with endometrial cancer cell lines HEC1-A and KLE expressing wild-type PTEN as the control.
These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of body mass index, and provide a potential explanation for discrepant reports on the effect of PTEN status and obesity on prognosis in endometrial cancer.
Three different human endometrial cancer cell lines known to have wild-type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies.