TGF-beta-induced factor homeobox 2（TGIF2）基因位於第20對染色體20q11.2-q12位置，在先前研究發現，TGIF2會經由招募histone deacetylases和經由TGIF binding site在TGF-β路徑產生抑制轉錄作用，且有文獻指出在卵巢癌中發現TGIF2基因有大量表現情形。但TGIF2基因在肺癌的角色目前尚未有研究指出，所以本實驗室利用real-time PCR檢測肺癌病人組織TGIF2表現量，發現正常組織表現量高於腫瘤組織，且在肺癌細胞生長試驗、群落形成、細胞轉型試驗及細胞週期變化中，我們發現當使用HA-TGIF2載體促使TGIF2表現時會降低細胞生長。且依據轉型生長試驗，抑制TGIF2會增強細胞的轉型能力且促進TGIF2表現則會使轉型能力變差。而TGIF2會藉由細胞凋亡及調控細胞G1期以控制細胞生長速度，且TGIF2過度表現細胞會誘導細胞凋亡且降低在G1期的比例。在轉移試驗中，我們發現TGIF2可增加轉移能力而且使細胞型態改變。接著進行細胞侵潤試驗，發現當TGIF2過度表現時侵潤能力上升，但在CH27干擾抑制TGIF2者則無影響。並且我們發現TGIF2可能經由抑制JNK路徑來調控生長。最後我們利用動物模式觀察到過度表現TGIF2會抑制腫瘤的生長能力。綜合以上結果，TGIF2在部份肺癌細胞株中可能扮演了降低細胞增生及細胞轉型能力，但此現象並不存在於轉移及侵潤試驗。
TGF-beta-induced factor homeobox 2 (TGIF2) gene lies in the chromosome 20q11.2-q12 position. TGIF2 will recruit histone deacetylases and repress TGF-β-induced transcription via TGIF binding site. It has been reported TGIF2 gene has high expression level observed in ovarian cancers. The role of TGIF2 in lung cancer tumorigenesis is unknown. Our laboratory used real-time PCR to measure the TGIF2 gene expression level in lung cancer patient tissues, and that mRNA level of TGIF2 gene in normal tissues is higher than tumor tissues. In this study, we did the following experiments: cell growth assay, colony formation, anchorage-independent growth assay, cell cycle distribution and animal experiment. We found out when we used HA-TGIF2 vector to promote TGIF2 expression, it would decrease cell growth. According to anchorage-independent growth assay, reduced TGIF2 expression has better effect in cell transformation and enhanced TGIF2 expression has worse effect in cell transformation. And TGIF2 overexpressed cells will induce apoptosis and decrease the percentage in G1 phase. In the experiments of metastasis, we found that TGIF2 could increase migration and change cell shape. In invasion assay, TGIF2 overexpressed cells could increase invasive ability but TGIF2 knockdown cells doesn’t have such effect. Also, TGIF2 gene may modulate JNK pathway to affect lung cancer cell growth. In animal model, the decreased ability of tumor growth was observed in TGIF2 overexpressed cells. In conclusion, TGIF2 may play a role in reducing cell proliferation, cell transformation but not in metastasis and invasion in some lung cancer cell lines studied here.
