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Expressions of 14-3-3 gamma in Human Malignant Brain TumorsKao, Chiu-li 09 September 2004 (has links)
The family of 14-3-3 proteins is crucial for various physiological cellular processes such as signaling, cell growth, division, differentiation, and apoptosis. One of the 14-3-3 proteins members, 14-3-3 gamma, is abundantly expressed in brain and had been detected in the cerebrospinal fluid of
patients with different neurological disorders. Although 14-3-3 gamma played critical physiological or pathological role in brain, it has not been reported on brain tumorigenesis. To test expression of 14-3-3 gamma in brain tumor, 3 brain tumor cell lines and 4 normal brain tissues, 24 astrocytoma, 14 glioblastoma mutiform, 2 oligodenroglioma, 1 ependymoma were analyzed using RT-PCR, western blotting, immunohistochemistry, real-time quantitative PCR. The study found that the expressions of 14-3-3 gamma mRNA in all of tumor three cell lines was greater than normal brain tissue, but the 14-3-3 gamma proteins expressed were lower than normal brain tissue. In brain tumor tissues, higher 14-3-3 gamma mRNA expression was detected in 20 of 24 astrocytoma (83%) and higher 14-3-3 gamma protein expression was detected in 9 of 24 astrocytoma (37%). The expression of 14-3-3 gamma mRNA is higher than normal brain tissue in all 14 glioblastoma multiforme (100%), and the 14-3-3 gamma protein was expressed higher in 9 of 14 glioblastoma multiforme than normal brain tissue (64.3%). Besides, the 14-3-3 gamma protein expressed much higher in glioblastoma multiforme than astrocytoma .The copy number of the 14-3-3 gamma gene was higher in astrocytoma and glioblastoma multiforme than normal brain tissue. Thus, this study evidenced that the 14-3-3 gamma protein may play a crucial role during tumorigenesis of brain tumors.
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Overexpression of 14-3-3 gamma protein in human breast carcinomaChen, Chien-min 07 July 2004 (has links)
The chaperone proteins designated 14-3-3 are expressed in all eukaryotic cells; they help to regulate signal transduction pathways controlling proliferation, differentiation, and survival. They associated directly or indirectly with proliferative signal-transducing proteins such as PKC, MEK kinases, PI3-kinase and Raf. In human, there are seven isotypes of 14-3-3 genes: £]¡]beta¡^¡B£^¡]gamma¡^¡B£`¡]epsilon¡^¡B£b¡]eta¡^¡B£m¡]sigma¡^¡B£n/£c¡]tau/theta¡^ and£a¡]zeta¡^, some of which would be pseudogenes, and yeast and plant each have two and fifteen genes. Althought these genes are diverse, all 14-3-3 isotypes share many conservation domains in amino acid sequences.
The previous studies have suggested that 14-3-3 sigma is most directly linked to cancer because it is thought to function as a tumor suppressor by inhibiting cell-cycle progression. In tumor formation, inactivation of 14-3-3 sigma occurs with high frequency. More importantly, expression of 14-3-3 sigma is silenced in most breast cancer cells. The 14-3-3 sigma protein is associated with cyclin E-CDK2 complex as well as cyclin B-CDC2 complex and mediated their inactivation by cytoplasmic localization and causing cell-cycle arrest in G2 and G1. However, the roles of other 14-3-3 isotypes in the formation of breast cancer are controversial in published reference.
The aim of this study was to determine the differential expressions of 14-3-3 gamma in non-tumor tissues and corresponding tumor tissues. Amplification and overexpression of 14-3-3 gamma in DNA, RNA, and protein of breast tumor tissues were found by experiments of RT-PCR, Western blot analysis, immunohistochemistry and Real-time PCR. However, the role of 14-3-3 gamma in the formation of breast cancer requires further study.
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