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Syndecan-1, a key regulator of cell viability in endometrial cancer.

Choi, DS; Kim, JH; Ryu, HS; Kim, HC; Han, JH; Lee, JS; Min, CK
International journal of cancer, 121(4):741-750, 2007
Journal Title
International journal of cancer
Syndecan-1 is one of the major proteoglycans on cell surfaces involved in major biological processes. Although loss of syndecan-1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan-1 also coincides with adverse outcomes in some cancers, including breast, ovarian and pancreatic cancers. For this Janus-faced attitude of syndecan-1, we sought to examine expression patterns of syndecan-1 in endometrial carcinoma (EC) and gain insight into the roles of syndecan-1. Immunohistochemical examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC uteri revealed that syndecan-1 expression was significantly upregulated in EC compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions of syndecan-1, its expression level was altered, and subsequent outcomes were examined using human endometrial cancer cell lines such as HEC-1A, AN3CA and KLE cells. Overexpression of syndecan-1 increased the growth of HEC-1A cells regardless of anchorage dependence while silencing syndecan-1 by antisense RNAs caused apoptotic cell death. Consistent with decreased viability, the loss of syndecan-1 was also accompanied by a decrease in the activation of Erk and Akt and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are known as negative and positive regulators of Akt activation, respectively. These down-regulatory effects were reversed upon overexpression of syndecan-1. Collectively together, the aforementioned findings lend support to the notion that upregulation of syndecan-1 may be a critical element for endometrial cancers in maintaining their viability and thus can serve as a cancer specific therapeutic and diagnostic marker.
MeSH terms
ApoptosisCell LineCell Line, TumorCell Survival*Endometrial Neoplasms/metabolism*Endometrial Neoplasms/pathologyEndometrium/metabolism*Extracellular Signal-Regulated MAP Kinases/metabolismFemaleHumansImmunohistochemistryPTEN Phosphohydrolase/metabolismPhosphorylationProto-Oncogene Proteins c-akt/metabolismRNA InterferenceSignal TransductionSyndecan-1/physiology*Up-Regulation
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Obstetrics & Gynecology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
AJOU Authors
유, 희석한, 재호
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