Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bax and Bcl-2 are a pair of important genes that control programmed cell death, or apoptosis, with Bax being the apoptosis promoter and Bcl-2 the apoptosis protector. Although the detailed mechanism is unknown, the protein products of these two genes form protein dimers with each other and the relative ratio of the two proteins is believed to be a determinant of the balance between life and death. In our preliminary study, we found that K562 erythroleukemia cells have an extremely low level of endogenous Bcl-2 expression and a fairly high level of endogenous Bax expression. We constructed Bax and Bcl-2 expression vectors and transfected them into K562 cells. We found that transfection of Bax vector increased the expression of Bax protein; a shortened form of Bax also appeared. Cell death analysis using the Annexin V assay showed that the Bax vector caused significantly more apoptotic cells that the Bcl-2 or pCI-neo vector did. After selection with G418, Bax, Bcl-2 and pCI-neo stably transfected cells were established. These three cell lines were examined for their response to the chemotherapeutic agents ara-C, doxorubicin, etoposide and SN-38. Bax-K562 cells showed significantly higher fractions of apoptotic cells than pCI-neo-K562 cells when treated with ara-C, doxorubicin or SN-38. No sensitization effect was seen when etoposide was used. In contrast, Bcl-2-K562 cells had fewer apoptotic cells than pCI-neo-K562 cells after treatment with all these agents. Therefore, Bax may sensitize K562 cells to apoptosis induced by a wide range of, but not all, chemotherapeutic agents.
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PMID:Overexpression of Bax gene sensitizes K562 erythroleukemia cells to apoptosis induced by selective chemotherapeutic agents. 956 26

The aim of the current study was to evaluate the expression of microRNA (miR)-17 in the endometrial tissues of patients with adenomyosis (AM) and determine its biological function in the occurrence and development of the disease. A total of 45 fresh endometrial tissues of AM patients and 32 normal endometrial tissues were collected from healthy controls. The expression of miR-17 was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The miR-17-targeting gene phosphatase and tensin homolog (PTEN) was predicted using bioinformatics and its expression was evaluated with RT-qPCR and western blot analysis. Endometrial cells were isolated from patients with AM and healthy controls. They were cultured in vitro and transfected with antagomiR-17 to downregulate miR-17 expression, subsequently cell viability and apoptosis were measured using MTT and flow cytometry. The expression of PTEN and cell cycle- and apoptosis-related proteins were evaluated using western blot analysis. Endometrial cells that stably overexpressed PTEN were screened in vitro by co-culture with G418. A dual-luciferase reporter assay was conducted to verify whether miR-17 was directly bound to PTEN mRNA. The results demonstrated that expression of miR-17 was significantly increased in the endometrial tissues of patients with AM compared with control patients (P<0.05). PTEN mRNA and protein expression were significantly lower in the AM group compared with the control group (P<0.05). When the expression of miR-17 in the cells was downregulated, the expression of PTEN was significantly increased (P<0.05). In addition, expression of Bcl-2 protein was significantly decreased and that of Bax protein significantly increased compared with the negative control (both P<0.05). The expression of cyclins E1 and D1 were also significantly downregulated (P<0.05). When PTEN was overexpressed or miR-17 was downregulated, the viability of endometrial cells significantly decreased and cell apoptosis significantly increased (all P<0.05). A dual-luciferase reporter assay indicated that miR-17 could directly bind to the PTEN mRNA 3'-untranslated region to regulate its expression. Thus the current study indicates that expression of miR-17 was increased in the endometrial tissues of patients with AM and may influence cell apoptosis and cyclin expression through the targeted regulation of PTEN. These results suggest that miR-17 promotes the occurrence and development of AM.
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PMID:MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence and development of adenomyosis. 2904 83