第一類轉型生長因子（TGF-α）在人類非小細肺癌細胞株的表現與自泌刺激效應

正常細胞或轉形細胞中，第一型轉形生長因子（transforming growth factor-α；TGF-α）表現出可調控多項細胞反應的能力。先前我們發現，人類非小細肺癌細胞株（NSCLC）大量表現上皮生長因子受體（EGF receptor），TGF-α結合EGF receptor後可刺激細胞活化而增殖。本文則仔細探討以TGF-α為主的自泌刺激（autocrine）對這些細胞的影響。以NSCLC之巨大細胞癌細胞株H460，腺細胞癌細胞株H322、H358、CL-1，扁平細胞癌細胞株H226及H226腦轉移細胞株-H226Br為材料，取RNA進行反轉錄聚合鍊反應（RT-PCR），觀察細胞中TGF-α transcript的表現。結果顯示，TGF-α transcript表現量以H322及H358最高，H226、H226Br次之，H460再次之，CL-1最少。此外，在無血清培養液中加入TGF-α後，可對各細胞株造成不同程度的刺激效應（mitogenic effect）。其中對非小細肺癌細胞株H226、H226Br、H322及H460細胞株有顯著促進不同程度刺激效果。以10 ng/ml TGF-α刺激1 × 10^4細胞時，H322增殖率增加26.1%、H460則增加11.7%。H226細胞增殖率增加24.4%、H226Br增加46.5%。此結果顯示，人類NSCLC細胞株中，自身分泌TGF-α扮演著不同的刺激調控角色。由反轉錄聚合鍊反應結果顯示，H226Br細胞中TGF-α transcript表現較母細胞H226少，但EGF receptor表現量卻為H226的二倍，外加TGF-α引起的刺激效應遠高於H226，顯示扁平癌細胞在轉移腦後，於分泌TGF-α的微環境中，H226Br有效分泌運用少量TGF-α刺激大量高親合EGF receptor所產生高度自泌刺激效應。H226細胞株在無血清、無EGF培養液中，外加TGF-α刺激不但促進細胞增殖，同時也使細胞內TGF-α transcript量增加。實驗結果顯示TGF-α對H226細胞中TGF-α基因表現有自我調控作用，而H226Br細胞則無此調控作用。

關鍵字

第一類轉形生長因子；自泌刺激效應；人類非小細肺癌細胞

並列摘要

Transforming growth factor-α (TGF-α) is a pleiotropic factor mediating cell responses in normal and transformed cells. They include cellular differentiation, proliferation, migration, and formation of extracellular matrix of cells. Epidermal growth factor receptor (EGF receptor) was shown overexpressed in non-small cell lung cancer (NSCLC) cell lines. The receptors are active as demonstrated in immune complex kinase assays. In this work, we studied the production and the biological response of TGF-α by human NSCLC cell lines H226 (squamous cell carcinoma cells), H322, H358, CL-1 (adenocarcinoma cells), H460 (large cell carcinoma cells), and 226Br- a brain metastatic variant of H226. All cell lines studied expressed different levels of TGF-α transcripts as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cell lines H322 and H358 cells were shown to have the highest TGF-α transcript level; whereas CL-1 has the lowest. In H226Br, the expressed TGF-α transcripts is lower than H226; Exogenous TGF-α stimulates dose-dependent cell proliferation with the optimal concentration at 10 ng/ml. At this concentration, the growth of H226, H226Br, H322, and H460 cells are increased by 24.4 %, 46.5 %, 26.1 %, and 11.7 %, respectively. The results indicated that TGF-α is an important autocrine growth stimulator for human NSCLC cell lines. TGF-α transcripts in H226Br is less than that of the parental cells H226, whereas high-affinity EGF receptors in H226Br is higher than that of H226, thereby increasing mitogenic effect of TGF-α on H226Br cells. The data also suggest that TGF-α-mediated autocrine/paracrine mechanism in the brain metastatic variant H226Br is more important than that in the parental cells H226. Furthermore, in the presence of 10 ng/ml TGF-α, H226 TGF-α gene expression was found induced in H226, suggesting the presence of TGF-α gene autoinduction in human NSCLC cells.

並列關鍵字

Transforming growth factor-α ； Autocrine ； Non-small cell lung cancer

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第一類轉型生長因子（TGF-α）在人類非小細肺癌細胞株的表現與自泌刺激效應

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