PDF(Pubmed)
Abstract：
Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell-cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.
摘要：
癌症是在一个多步骤的过程中发展的，其中环境致癌暴露是主要的病因成分，细胞间的通讯支配着组织的生物活动。鉴定调节这一过程的分子基因对于靶向转移性乳腺癌至关重要。电离辐射可以修饰和损伤DNA，RNA,和细胞膜成分如脂质和蛋白质通过直接电离。比较差异基因表达可以帮助确定辐射和雌激素对细胞粘附的影响。通过将永生化人乳腺上皮细胞系MCF-10F暴露于低剂量的高线性能量转移α粒子辐射并随后在17β-雌二醇的存在下生长，开发了体外实验性乳腺癌模型。MCF-10F细胞系在转化的不同阶段进行了分析，显示出逐渐的表型变化，包括改变的形态，细胞增殖相对于对照增加，锚定独立生长，在裸鼠中形成肿瘤之前的侵袭能力。该模型用于确定与细胞粘附和通讯相关的基因，例如E-cadherin，桥粒蛋白3，间隙连接蛋白α1，整合素α6，整合素β6，角蛋白14，角蛋白16，角蛋白17，角蛋白6B，还有层粘连蛋白β3.结果表明，大多数基因在来自无胸腺动物的致瘤细胞系Tumor2中的表达高于Alpha3，一种仅暴露于辐射的非致瘤细胞系，表明粘附分子表达水平的改变取决于雌激素。非常需要促进细胞可塑性研究的实验模型系统，以评估雌激素在调节癌细胞生物学中的重要性。
