Birrer M J, Alani R, Cuttitta F, Preis L H, Sabich A L, Sanders D A, Siegfried J M, Szabo E, Brown P H
National Cancer Institute-Navy Medical Oncology Branch, National Naval Medical Center, Bethesda, Md 20895.
J Natl Cancer Inst Monogr. 1992(13):31-7.
The complex process of epithelial carcinogenesis is composed of discrete biologic events including the early activation events of "initiation" and "promotion." For lung cancer, these events are only now being elucidated. Despite the identification of possible target genes and their mutations, the "initiation" events for lung cancer remain poorly understood. The identification of these "initiation" events is a crucial step toward the development of practical molecular markers for early detection of this disease. The reversible process of tumor promotion remains somewhat enigmatic but is a promising target for chemoprevention. A wide range of substances, including asbestos and various substances in cigarette smoke, behave as tumor promoters for lung cancer. They appear to promote tumor formation by inducing cellular proliferation mediated in part by growth factors. The intracellular signals these factors provide are ultimately translated into cellular growth via steps involving nuclear transcription factors. Early response genes such as the jun and fos gene family members encode such nuclear transcription factors which are expressed in lung cancer cells and primary bronchial epithelial cells. The expression of these transcription factors is highly responsive to stimulation by growth factors including serum, transforming growth factor, and gastrin-releasing peptide. A more thorough understanding of this process will allow the development of molecular and/or pharmacologic antagonists that can interfere with the biologic process of tumor promotion and therefore function as chemoprevention agents.
上皮细胞癌变的复杂过程由一系列离散的生物学事件组成，包括“启动”和“促进”等早期激活事件。对于肺癌来说，这些事件目前才刚刚开始被阐明。尽管已经确定了可能的靶基因及其突变，但肺癌的“启动”事件仍知之甚少。确定这些“启动”事件是开发用于早期检测该疾病的实用分子标志物的关键一步。肿瘤促进的可逆过程仍然有些神秘，但它是化学预防的一个有前景的靶点。多种物质，包括石棉和香烟烟雾中的各种物质，都可作为肺癌的肿瘤促进剂。它们似乎通过诱导部分由生长因子介导的细胞增殖来促进肿瘤形成。这些因子提供的细胞内信号最终通过涉及核转录因子的步骤转化为细胞生长。早期反应基因，如jun和fos基因家族成员，编码此类核转录因子，它们在肺癌细胞和原发性支气管上皮细胞中表达。这些转录因子的表达对包括血清、转化生长因子和胃泌素释放肽在内的生长因子的刺激高度敏感。对这一过程的更深入理解将有助于开发分子和/或药物拮抗剂，这些拮抗剂可以干扰肿瘤促进的生物学过程，从而起到化学预防剂的作用。
