Expression of p21(WAF1) is related to acetylation of histone H3 in total chromatin in human colorectal cancer

Abstract

Aim: To explore the relationship between acetylation of histone in total chromatin and p21(WAF1) expression regulation in human colorectal carcinoma.

Methods: 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.

Results: 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.

Conclusion: 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.

Figure 1

RT-PCR products of grouped samples of colorectal cancerous tissues (lanes 1, 4, 7, 10), corresponding para-cancerous tissue (lanes 2, 5, 8, 11) and normal colorectal mucosa (lanes 3, 6, 9, 12). β-actin amplified from the same cDNA served an internal control.

Figure 2

Level of acetylated core histone H3 (A) and mRNA p21^WAF1 mRNA (B) in colorectal carcinoma tissues. Lanes 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37: tumor tissue; lanes 2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38: corresponding para-cancerous tissue; and normal colorectal mucosa lanes 3, 6, 9, 12, 15, 18, 21, 34, 27, 30, 33, 36, 39: normal colorectal mucosa.