Published online Oct 15, 1998. doi: 10.3748/wjg.v4.iSuppl2.138
Revised: August 16, 1998
Accepted: September 12, 1998
Published online: October 15, 1998
AIM: The INK4a tumor suppressor gene locus on human chromosome 9 p21 encodes two unrelated proteins: p16 INK4a, a specific inhibitor of the cyclin D-dependent kinases CDK4 and CDK6, and p19ARF, an alternative reading frame protein which can also induce cell cycle arrest in G1/S and G2/M transition. Inactivation of p16INK4 is a frequent event in various human tumors; mice lacking p19ARF develop tumors early in life. The specific aim for this study was to investigate the possible role of p19ARF and its relationship with other tumor suppressor gene p53 and p21 in esophageal carcinogenesis.
METHODS: RT-PCR was used to measure the expression of p19A RF, p53 and p21 in 19 pairs of frozen normal esophageal and tumor samples. The cycle number for each pair of primers was fine-tuned to limit the amplification to a linear range. PCR products were then resolved on 2% agrosegel. The density and area of each band was measured using image-pro-plus 1.3 software. The relative expression level of each gene in tumor and normal was calculated using the housekeeping gene GAPDH as an internal control.
RESULTS: In the total of 19 tumor samples, 8(42) had at least a 3-fold decrease in p19ARF but with no decrease in p53 expression, 5(26%) had significantly decreased expression of p53 but had normal expression of p19ARF, only two samples (11%) had decreased level in both p19ARF and p53 expression. The results suggest a negative correlation between the alterations of these two genes in the esophageal tumor. The relative expression level of p21 in p19ARF negative sample (0.78 ± 0.16) is about half of that in p19ARF positive samples (1.63 ± 0.22).
CONCLUSION: Our results support the hypothesis that p19 inactivation contributes to esophageal tumor progression and follows the same pathway as p53 and p21.