Forkhead transcription factor FOXO1 is a direct target of progestin to inhibit endometrial epithelial cell growth.

Purpose And Experimental Design: Despite the therapeutic utility of progestin in invasive and preinvasive endometrial neoplasias, the molecular mechanisms through which it exerts inhibitory effects on endometrial epithelial growth are largely unknown. The aim of the study was to clarify the molecular mechanisms of progestin action to endometrial epithelial cells using originally established in vitro and in vivo treatment models for immortalized and transformed endometrial epithelial cell lines that express progesterone receptor.

Results: In this model, progestin effectively inhibited the cell growth, inducing G0/G1 arrest rather than apoptosis without p21/WAF-1 induction.

Diagnostic potential and limitation of imaging cancer cells in cytological samples using telomerase-specific replicative adenovirus.

Cytological cancer screening that targets genetic or epigenetic abnormalities may be a viable alternative to morphological screening. Detecting cancer cells by specific genetic markers helps their easy detection in cytological samples. We recently established the telomerase-specific replication-selective adenovirus OBP-401, in which the human telomerase reverse transcriptase (hTERT) gene promoter has been inserted upstream of the E1 genes, and in which the green fluorescent protein (GFP) gene is driven by the CMV promoter.

Role of menin in the regulation of telomerase activity in normal and cancer cells.

Transcriptional activation of human telomerase reverse transcriptase (hTERT) is critical for telomerase expression, a major step for cellular immortality and carcinogenesis. Although several transcriptional activators have been identified, factors responsible for repressing the hTERT promoter are largely unknown. Gene screening that employed enhanced retroviral mutagenesis has identified potential hTERT repressors.

Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosiss.

Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear. In the present study, we examined the status of the PI3K signaling pathway, especially in relation to PTEN and PIK3CA status, in endometrioid-type endometrial cancer. The immunohistochemical analysis revealed a high level of phosphorylated (p)-AKT expression, which is a hallmark of activated PI3K signaling, in approximately 60% of endometrial cancers.

Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis.

The extracellular-regulated kinase (ERK) signaling pathway plays important roles in regulating the malignant potential of cancer cells in vitro. However, the effect of ERK signaling on the prognosis of human tumors is not clearly understood. The present study examined the expression of phosphorylated ERK1/2 (p-ERK1/2) as a hallmark of ERK activation, in relation to KRAS and BRAF mutations, in 63 endometrial cancer specimens with endometrioid-subtype, in order to clarify the prognostic value of p-ERK1/2 expression.

High Twist expression is involved in infiltrative endometrial cancer and affects patient survival.

Epithelial-mesenchymal transition (EMT) is critical not only for morphogenesis during embryonic development but also the conversion of early-stage tumors into infiltrative phenotypes. The present study examines the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluated its prognostic significance in endometrial cancers. Tissue specimens from 70 patients with endometrial cancer who underwent primary surgery were immunohistochemically evaluated for Twist expression.

Aberrant expression and mutations of TGF-beta receptor type II gene in endometrial cancer.

Objective: Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that strongly inhibits epithelial cell growth. Disabling of TGF-beta signaling is thought to be involved in development of a variety of tumors in which abnormal expression or function of TGF-beta receptor plays critical roles. In the present study, we examined aberrant expression and mutation of the gene TGF-beta receptor type II (TbetaRII) in endometrial cancers of endometrioid subtype.

Association of mismatch repair deficiency with PTEN frameshift mutations in endometrial cancers and the precursors in a Japanese population.

We studied mismatch repair deficiency and PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutations in endometrial cancers and hyperplasias in a Japanese population. Methylation-sensitive restriction enzyme polymerase chain reaction revealed MLH1 hypermethylation in 21 (38%) of 56 endometrial cancers. Sequencing analysis revealed PTEN mutations in 22 patients with cancer (39%) in exons 5 and 8.

Analysis of telomeric single-strand overhang length in human endometrial cancers.

The 3' single-strand telomeric overhang (3'-OH) is a key component of telomere structure. Although telomere length has been well analyzed in a variety of human cancers, no information is available on the 3'-OH length in cancers. In the present study, we examined the 3'-OH length in normal and malignant endometria using telomere-oligonucleotide ligation assay.