Title

探討PRL3在非小細胞肺癌中對侵襲及腫瘤生成的影響

Translated Titles

Study of PRL3 on invasion and tumorigenesis in non-small-cell lung carcinoma

DOI

10.6845/NCHU.2010.00147

Authors

李岳勳

Key Words

PRL3 ; 肺癌 ; 微陣列分析 ; PRL3 ; lung cancer ; microarray

PublicationName

中興大學生物醫學研究所學位論文

Volume or Term/Year and Month of Publication

2010年

Academic Degree Category

碩士

Advisor

陳健尉

Content Language

繁體中文

Chinese Abstract

PRL3屬於phosphatase of regenerating liver (PRL)家族蛋白之ㄧ,為酪胺酸去磷酸酶。根據最近的研究指出,在大腸直腸癌中表現較高的PRL3會促進轉移與癌症發展進程,同時,在其它不同的癌症中例如:乳癌、胃癌、卵巢癌等癌症中,大量表現PRL3同樣會促進癌細胞增生、移動、侵襲能力。肺癌是目前世界上發生率與死亡率快速增加的癌症之ㄧ,近年來在台灣,肺癌也已躍居死亡率的前幾位,然而PRL3在肺癌上扮演的角色與功能仍未被詳細研究。為了瞭解PRL3與肺癌的相關性,首先將PRL3構築在pCMV-Tag 3B上,同時設計構築PRL3突變型C104S與C170S,確認在SW480大腸癌細胞株中大量表現PRL3時會促進侵襲能力,反之,表現PRL3 C104S時則會回復侵襲能力。接著進一步在CL系列的肺癌細胞株中觀察PRL3的表現量,發現侵襲能力較弱的細胞株CL1-0,PRL3表現量較高,而侵襲能力較強的細胞株CL1-5,PRL3的表現量較低。根據此結果我們將pCMV-Tag 3B-PRL3送入CL1-5細胞株中,觀察大量表現PRL3時,會明顯地抑制CL1-5的侵襲、移動、聚落形成的能力,反之,利用大量表現PRL3 C104S與C170S的突變型,則發現CL1-5的侵襲能力會增強。此外,我們也利用活體動物實驗,將CL1-5對照組與大量表現PRL3的細胞從皮下注射到裸鼠中,經過四週後,將裸鼠犧牲,觀察大量表現PRL3的細胞株腫瘤生成的能力明顯受到抑制。最後,透過微矩陣分析對照組細胞與大量表現PRL3的細胞,觀察基因的表現差異,經由路徑分析挑選表現有差異的基因,再以即時定量連鎖聚合酶反應確認表現差異。綜合以上的結果PRL3可能參與調控肺癌細胞侵襲與移動的機制,使得CL1-5細胞侵襲與移動能力下降,這與先前在大腸癌等癌症中的功能不同,本研究提供PRL3不同功能上的研究,期望PRL3的研究機制更為透徹。

English Abstract

Phosphatase of regenerating liver 3 (PRL3) is a member of PRL protein tyrosine phosphatase family. Recent reports indicated that high level of PRL3 expression might be involved in colorectal cancers tumorigenesis and metastasis. In other cancers like breast carcinomas, gastric carcinomas and ovarian cancers, overexpression of PRL3 would similarly promote cell proliferation, migration and invasion. In recent years, lung cancer became one of the most serious cancers. In Taiwan, lung cancers also caused highly incidence rate and fatality rate. However, little is known about PRL3 function in lung cancer. In order to investigate the correlation between PRL3 and lung cancer, first we confirmed overexpression of PRL3 in SW480 would promote invasion, and overexpression of catalytic PRL3 mutant (C104S) effectively diminished the PRL-3-mediated invasion, as previous study. In lung cancer, we found that PRL3 expression in CL1-5, a highly invasive cell line, was lower than CL1-0, a lowly invasive cell line. Overexpression of PRL3 in CL1-5 remarkable inhibition capability of proliferation, migration, invasion, and colony formation compared with mock cells. Conversely, overexpression of catalytic PRL3 mutant (C104S) and PRL3 mutant (C170S) would enhance cell invasion. Furthermore, nude mice were subcutaneous injection with CL1-5 cells transfected with empty vector or c-myc-PRL3 vector. Twenty-eight days later, less tumorigenesis was found in mice injected with c-myc-PRL3 transfected cells than with mock cells. Finally, we surveyed gene expression between mock cells and PRL3-overexpression cells by microarray, and we focused on focal adhesion and related adhesion molecules via preliminary analysis possible pathway regulated by PRL3. Taken together, PRL3 might play a role of tumor suppressor in lung cancer, which is different from other cancers.

Topic Category 醫藥衛生 > 基礎醫學
生命科學院 > 生物醫學研究所
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