Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression in human endometrial cancer tissues and serous papillary endometrial cancer cell line, SPAC-1L, treated by STAT1-siRNA and/or IFN-gamma

ABSTRACT: Endometrial cancer is one of the most common gynecologic malignancies, and patients with high grade disease, especially serous papillary subtype (SPEC) are often related to the poor outcomes. Recent genome-wide analyses have revealed that SPEC exhibits gene expression profiles that are distinct from the endometrioid histologic subtype; therefore, it is important to identify the SPEC driver genes or pathways responsible for the inherently aggressive phenotypes and to develop SPEC-specific therapies to target these driver genes or pathways. Through array-based analysis and immunohistochemical staining of human endometrial cancer tissue, STAT1 is identified high expressed, and can distinguish SPEC from other subtypes of endometrial cancer. In vitro and in vivo experiments show STAT1 role as a pro-survival factor in SPEC. STAT1 was identified as a master gene modulating “transcriptional pro-survival pathways” to enhance multiple malignant characteristics These finding may suggest that targeting of STAT1, the SPEC driver gene, may provide the means to improve poor outcomes for patients with SPEC. We used microarrays to clarify the changes of gene expression along with STAT1-siRNA treatment and to confirm whether there are any changes on genes expression related to STAT1 pathway. We also used the microarray data to clarify genes signatures which can distinguish subtype of human endometrial cancers.

ORGANISM(S): Homo sapiens

SUBMITTER: Budiman Kharma

PROVIDER: E-GEOD-56026 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

STAT1 drives tumor progression in serous papillary endometrial cancer.

Kharma Budiman B Baba Tsukasa T Matsumura Noriomi N Kang Hyun Sook HS Hamanishi Junzo J Murakami Ryusuke R McConechy Melissa M MM Leung Samuel S Yamaguchi Ken K Hosoe Yuko Y Yoshioka Yumiko Y Murphy Susan K SK Mandai Masaki M Hunstman David G DG Konishi Ikuo I

Cancer research 20140929 22

Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition o ...[more]

PMID: 25267067

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Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in women after breast, lung and colorectal cancer. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer is on the rise. Considerable research effort has therefore been placed on understanding the pathogenesis of this disease to combat this growing issue. There is now emerging evidence to suggest a putative role for dysregulation of the renin angiotensin system (RAS) and in particular the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. Support for this notion arises from previous literature implicating (P)RR in cancer pathophysiology (e.g., breast cancer and pancreatic carcinoma) by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. In view of these data, we aimed to investigate the functional role of (P)RR in human endometrial cancer progression and development. To this end, we employed an siRNA-mediated knock down approach to abrogate (P)RR expression in the immortalized endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1A to explore the role of (P)RR in cellular proliferation and cellular viability. To further extend these analyses we also carried out a sophisticated proteomic screen, that investigated the potential pathways via which (P)RR is acting in endometrial cancer physiology. These data confirmed that (P)RR is critical for endometrial cell cancer development, contributing to both its proliferative capacity and in the maintenance cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets in the treatment of this cancer. Finally we contend that (P)RR, in its soluble form (s(P)RR) in blood, may have substantial potential as a novel biomarker for cancer diagnosis and prognosis prediction going forward.

Dataset Information

Gene expression in human endometrial cancer tissues and serous papillary endometrial cancer cell line, SPAC-1L, treated by STAT1-siRNA and/or IFN-gamma

Publications

STAT1 drives tumor progression in serous papillary endometrial cancer.

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