Chow V, Ang W
Int J Oncol. 1995 Apr;6(4):871-6. doi: 10.3892/ijo.6.4.871.
Entry into the cell cycle is governed by cyclins, cyclin-dependent kinases (CDKs) and CDK-inhibitors (CDKIs). The p53-regulated inhibitor of CDKs (PIC1) is a universal CDKI whose gene expression is directly induced by the p53 tumor suppressor protein. Reverse transcription and polymerase chain reaction revealed strong PIC1 gene expression in control MRC-5 human embryo lung cells, but relatively weaker bands in A549 lung carcinoma; Hep3B, Mahlavu, PLC/PRF/5 hepatocellular carcinoma; SiHa, CaSki, HeLa cervical carcinoma; T24 bladder carcinoma; MCF7 breast carcinoma; Raji Burkitt lymphoma; HT-1080 fibrosarcoma; and G-401 Wilms' tumor cell lines. These data are consistent with other results obtained by Northern and Western blot and immunoprecipitation techniques, indicating diminished PIC1 expression in cancer cells especially those harboring mutated p53, or human papillomavirus E6 oncoproteins which abrogate p53 activity. PIC1 gene expression was absent in the Molt-4 T-lymphoblastic leukemia cell line with a previously documented alternatively-spliced p53 transcript translating into p53 protein truncated at the carboxyl terminus. It is proposed that this aberrant p53 interferes with the binding of wild-type p53 and other transcription factors to the PIC1 promoter thereby abolishing PIC1 gene expression. This Molt-4 cell line could serve as a useful experimental system for studying the interaction between p53 and other cellular factors with the PIC1 gene. Single-strand conformation polymorphism and direct cycle DNA sequencing analyses demonstrated a PIC1 variant (with an AGC to AGA substitution at codon 31 culminating in a serine to arginine replacement) in Mahlavu, PLC/PRF/5, SiHa, A549 and Raji cell lines. The higher proportion of the PIC1 variant in cancer cell lines (5/13 or 38%) compared with normal individuals (14%), coupled with differences between the predicted secondary structures of the normal and variant PIC1 proteins merit further investigations to elucidate the biological significance of this variant.
细胞周期的进入受细胞周期蛋白、细胞周期蛋白依赖性激酶（CDK）和CDK抑制剂（CDKI）的调控。p53调节的CDK抑制剂（PIC1）是一种通用的CDKI，其基因表达由p53肿瘤抑制蛋白直接诱导。逆转录和聚合酶链反应显示，在对照MRC-5人胚肺细胞中PIC1基因表达强烈，但在A549肺癌细胞；Hep3B、Mahlavu、PLC/PRF/5肝癌细胞；SiHa、CaSki、HeLa宫颈癌细胞；T24膀胱癌细胞；MCF7乳腺癌细胞；Raji伯基特淋巴瘤细胞；HT-1080纤维肉瘤细胞；以及G-401肾母细胞瘤细胞系中条带相对较弱。这些数据与通过Northern印迹、Western印迹和免疫沉淀技术获得的其他结果一致，表明癌细胞中PIC1表达减少，尤其是那些携带p53突变或人乳头瘤病毒E6癌蛋白（其消除p53活性）的癌细胞。在Molt-4 T淋巴细胞白血病细胞系中不存在PIC1基因表达，该细胞系先前记录有一个选择性剪接的p53转录本，可翻译成羧基末端截短的p53蛋白。有人提出，这种异常的p53会干扰野生型p53和其他转录因子与PIC1启动子的结合，从而消除PIC1基因表达。该Molt-4细胞系可作为研究p53与其他细胞因子与PIC1基因之间相互作用的有用实验系统。单链构象多态性和直接循环DNA测序分析表明，在Mahlavu、PLC/PRF/5、SiHa、A549和Raji细胞系中存在一种PIC1变体（密码子31处发生AGC到AGA的替换，最终导致丝氨酸被精氨酸取代）。与正常个体（14%）相比，癌细胞系中PIC1变体的比例更高（5/13或38%），再加上正常和变体PIC1蛋白预测二级结构之间的差异，值得进一步研究以阐明该变体的生物学意义。
