新奇蛋白BC1促進細胞轉型之分析

A novel gene, BC1, contributes to oncogenic transformation in vitro and in vivo

周芳俞(Fang-Yu Chou)

指導教授 ： 李玉梅

國立臺灣大學/生命科學院/生化科學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01271

摘要

中文摘要
BC1是一個74KD的蛋白質，最初被發現在腦中，同時也在16個細胞株中被發現。先前的研究指出BC1能夠免除Huntingtin所誘導的聚集效應(aggregation)，同時也可以降低細胞毒性。
許多癌症的研究發現染色體20q13的位置大量增生會造成許多癌症的發生，例如：卵巢癌、乳癌、大腸癌、及胰臟癌。BC1正好座落在染色體20q13的位置。因此，我們想瞭解 (1) BC1是否具有致癌的特性？ (2) 是否抑制BC1可以降低腫瘤的形成？
首先，我們先建立能夠大量表現BC1的細胞株 (stable cell line)，我們發現在細胞實驗過程中，BC1會促進細胞增生及誘導細胞轉型。同時，在活體老鼠實驗中，BC1會導致腫瘤的生長。
其次，我們利用BC1的反意質體(antisense plasmid)來降低細胞株中BC1的表現量。結果發現，降低BC1的表現量可以有效抑制人類乳癌細胞的增生。
綜而言之，這些結果證實BC1與致癌能力及細胞存活能力有關，同時也證實BC1具有發展抗癌藥物的潛能。

關鍵字

致癌基因

並列摘要

We have isolated a novel gene, BC1, from the GCH (GTP cyclohydrogenase I) dominant negative cell models. BC1 is a 74KD polypeptide found in brain and also in 16 cell lines we tested. In the previous studies, BC1 could prevent Huntingtin induced aggregation as well as diminish cell toxicity.
Chromosome 20q13 has been identified as gene amplification in cancers such as ovarian, breast, colon and pancreatic carcinoma. BC1 resides in this region, thus, we are interested in (1) is BC1 oncogenic? (2) Whether the inhibition of BC1 reduces tumor progression?
In this study, we first established BC1 expression cell line and found that overexpression of BC1 exhibited significant advance of cell proliferation, induction transformation ability in soft agar assay, and stimulation of xenograft tumor growth in Nod-SCID mice.
Second, we generate BC1-knockdown cell lines by introducing BC1 antisense plasmid. Our results reveal that down-regulation of BC1 expression can effectively inhibit the proliferation of human breast cancer cells, and BC1 may serve as a drug target in carcinogenesis.
These results establish a role for BC1 in oncogenesis and cell survival and also demonstrate a potential strategy for cancer therapy.

並列關鍵字

oncogenic transformation

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