ABCG2a基因在斑馬魚胚胎發育中所扮演的角色

癌症病人治療時常常伴隨著抗藥性的產生，這點是在臨床上是非常困擾的。以乳癌病人為例，當腫瘤細胞對抗癌藥物產生抗藥性的時候，細胞膜上的ATP-binding cassette (ABC) 蛋白家族會大量表現，其中更以ATP-binding cassette, sub-family G member 2蛋白有明顯增多的趨勢。所以有非常多的科學家在探討抗藥性和ATP-binding cassette (ABC) 蛋白家族之間的關係，以及在發育過程中ABC蛋白家族所扮演的功能以及角色，藉此才能有效率地解決抗癌藥物治療失效化的問題。在本篇論文裡，我們利用Morpholino將斑馬魚胚胎中的zABCG2a基因進行knockdown之後，並觀察胚胎的生長和發育，發現在斑馬魚幼魚中有紅血球缺少的現象產生，我們進一步利用O-dianisidine 進行染色，觀察在不同的時間點 (36 hpf、48 hpf、60 hpf) 上血紅素的表現，發現在zABCG2a 基因knockdown後，斑馬魚胚胎上的血紅素有明顯受到抑制。觀察到此現象之後，我們使用聚合酶連鎖反應在zABCG2a knockdown後的斑馬魚胚胎上發現，scl、gata1早期造血基因的確有受到抑制使得紅血球表現受到影響，證明了zABCG2a基因可能在斑馬魚早期造血系統中扮演非常重要的角色。

關鍵字

多重抗藥性； ABC蛋白家族； ABCG2 ；造血幹細胞

並列摘要

MDR in cancer has lead to the failure of chemotherapeutic treatment in patients, it is difficult to solve in clinical trial. The over-expression of ABCG2 protein was observed in resistance breast cancer cell. It is very interest in ABC protein and MDR cell, in previous studies scientist want to understand that ABC protein play what is role in organic development. However, It is important to solve the MDR resistance in patients.In our study, we use zABCG2a MO knockdown zABCG2a mRNA expression, and observe embryo development in zebrafish embryo. Among the phenotype-induced by zABCG2a-MO knockdown, the diminished level of hemoglobin in yolk sac was most striking. we use O-dianisidine stain to detect hemoglobin expression in different time course (36 hpf, 48 hpf, 60 hpf). According to the result, hemoglobin are decrease by zABCG2a MO threat. To investigate the molecular mechanism of defective hemoglobin deposition caused by zABCG2a deficiency, the transcriptional regulation of hematopoiesis was exam. Using polymerase chain reaction Technology to analyze the zABCG2a MO knockdown zebrafish mRNA, scl and gata1 are found down-regulated by treatment. In our results showed that the transcript level of scl and gata1 was decreased in early embryo development. Taken together, these results suggest that zABCG2a play a important role in early embryo development.

並列關鍵字

MDR ； ABC protein ； ABCG2 ； hematopoiesis

參考文獻

Alestrom, P., J. L. Holter, et al. (2006). "Zebrafish in functional genomics and aquatic biomedicine." Trends Biotechnol 24(1): 15-21.

Amatruda, J. F. and L. I. Zon (1999). "Dissecting hematopoiesis and disease using the zebrafish." Dev Biol 216(1): 1-15.

Bodzioch, M., E. Orso, et al. (1999). "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease." Nat Genet 22(4): 347-351.

Chen, A. T. and L. I. Zon (2009). "Zebrafish blood stem cells." J Cell Biochem 108(1): 35-42.

Chen, Z., F. Liu, et al. (2010). "Suppression of ABCG2 inhibits cancer cell proliferation." Int J Cancer 126(4): 841-851.

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ABCG2a基因在斑馬魚胚胎發育中所扮演的角色

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