Chen Ying-Xuan, Fang Jing-Yuan, Lu Rong, Qiu De-Kai
Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease, 145 Shandong Zhong Lu, Shanghai 200001, China.
World J Gastroenterol. 2007 Apr 21;13(15):2209-13. doi: 10.3748/wjg.v13.i15.2209.
To explore the relationship between acetylation of histone in total chromatin and p21(WAF1) expression regulation in human colorectal carcinoma.
We analyzed the expression of tumor suppressor gene p21(WAF1) mRNA by RT-PCR or real-time PCR in 33 samples of colorectal cancerous tissue, corresponding para-cancerous tissue and normal colorectal mucosa, and also examined the level of acetylated histone H3 in total chromatin using Western blotting.
The expression level of p21(WAF1) mRNA was significantly lower in colorectal cancerous tissue from 33 patients than in para-cancerous tissue and normal colorectal mucosa (2377.95 +/- 865.80 vs 3216.58 +/- 1149.42 and 3541.61 +/- 1433.17 respectively, P < 0.01). In addition, when p21(WAF1) mRNA expression was undectectable or at very low level (50% less than that in adjacent tissue and normal colorectal mucosa) in all tissues, the level of acetylated histone H3 in colorectal cancerous tissue was significantly lower than that in corresponding para-cancerous tissue and normal colorectal mucosa in five of seven (71.43%) cases. The transcriptional level of p21(WAF1) in colorectal carcinoma might not be associated with its biological behaviors.
The down-regulation of p21(WAF1) transcription is involved in the tumorigenesis and development of colorectal carcinoma. The down-expression of p21(WAF1) mRNA in colorectal carcinoma might be associated with histone hypoacetylation in chromatin but not with biological behaviors.
探讨人结直肠癌全染色质中组蛋白乙酰化与p21（WAF1）表达调控之间的关系。
采用逆转录聚合酶链反应（RT-PCR）或实时荧光定量PCR分析33例结直肠癌组织、相应癌旁组织及正常结直肠黏膜中抑癌基因p21（WAF1）mRNA的表达，并运用蛋白质免疫印迹法检测全染色质中组蛋白H3乙酰化水平。
33例患者的结直肠癌组织中p21（WAF1）mRNA表达水平显著低于癌旁组织及正常结直肠黏膜（分别为2377.95±865.80、3216.58±1149.42和3541.61±1433.17，P<0.01）。此外，在所有组织中当p21（WAF1）mRNA表达未检测到或处于极低水平（比相邻组织和正常结直肠黏膜低50%）时，7例中有5例（71.43%）结直肠癌组织中组蛋白H3乙酰化水平显著低于相应癌旁组织及正常结直肠黏膜。结直肠癌中p21（WAF1）的转录水平可能与其生物学行为无关。
p21（WAF1）转录下调参与了结直肠癌的发生发展。结直肠癌中p21（WAF1）mRNA的低表达可能与染色质中组蛋白低乙酰化有关，而与生物学行为无关。
