Velculescu V E, El-Deiry W S
The Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
Clin Chem. 1996 Jun;42(6 Pt 1):858-68.
The p53 tumor suppressor gene controls cellular growth after DNA damage through mechanisms involving growth arrest and apoptosis. Mutations that inactivate p53 occur commonly in virtually all human malignancies and can be detected by sequencing of the p53 gene, immunohistochemical staining of tumor tissue with anti-p53 antibodies, single-strand conformation polymorphisms, or other biological assays. Identification of p53 mutation in the germ line is diagnostic of the cancer-prone Li-Fraumeni syndrome. Alterations of the p53 gene result in defective cellular responses after DNA damage and predispose cells to dysregulated growth, tumor formation and progression, and potential resistance (of tumor cells) to certain chemotherapeutic agents or ionizing radiation. A variety of tumors involving mutant p53 have a worse prognosis than tumors of the same type containing no p53 mutations. New diagnostic and therapeutic strategies are evolving as the p53 pathways of cell-cycle arrest and apoptosis become elucidated.
p53肿瘤抑制基因通过涉及生长停滞和凋亡的机制来控制DNA损伤后的细胞生长。使p53失活的突变几乎在所有人类恶性肿瘤中都普遍存在,可通过p53基因测序、用抗p53抗体对肿瘤组织进行免疫组织化学染色、单链构象多态性分析或其他生物学检测方法来检测。种系中p53突变的鉴定可诊断易患癌症的李-弗劳梅尼综合征。p53基因的改变导致DNA损伤后细胞反应缺陷,使细胞易于出现生长失调、肿瘤形成和进展,以及(肿瘤细胞)对某些化疗药物或电离辐射产生潜在抗性。与不含p53突变的同类型肿瘤相比,多种涉及突变p53的肿瘤预后更差。随着细胞周期停滞和凋亡的p53途径逐渐被阐明,新的诊断和治疗策略也在不断发展。