| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
Our series of recent study has demonstrated that there is a distinct difference between normal and malignant uterine cervical squamous epithelial tissues in the molecular heterogeneity of the tumor-related serine proteinase inhibitor (serpin), Squamous Cell Carcinoma (SCC) antigen. On the other hand, although maspin, identified as a 42-kDa unique tumor suppressive serpin in breast cancer, has multifaceted biological functions by interacting with various target molecules under physiological and pathological conditions including tumor progression, oxidative stress and so on, it is unknown what post-translational modification contributes the specific binding affinity of maspin to target molecules, such as glutathione S-transferase (GST). The aim of this study is therefore to analyze the molecular heterogeneity of maspin and identify its modification in MCF-10A cell, which is known to express abundant maspin protein, using various electrophoretic analyses. We successfully identified the novel form of endogenous maspin generated by intramolecular disulfide-bonded linkage under oxidative stress. Furthermore, glutathione beads pull-down assay revealed that intramolecular disulfide-bonded maspin lost the binding activity with endogenous GST, indicating that intramolecular disulfide-bonded maspin might have some distinct properties under oxidative stress, although the precise biological significance of this modification remains elusive. The western blot analysis using cervical primary cancer tissues showed that maspin expression levels in cervical cancer patients with pelvic lymph node metastasis were relative low compared to those with no pelvic lymph node metastases, suggesting that the suppression or post-translational modification of the tumor suppressive serpin, maspin might be related to tumor progression in cervical cancer.
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