Upregulation of non-mutated H-ras and its upstream and downstream signaling proteins in colorectal cancer

We analyzed H-ras protein expression in 38 human colon cancers and the pair ed normal tissues. H-ras levels were significantly higher in the malignant tumor (average 0.19 +/- 0.27) than in its normal adjacent tissues (average 0.06 +/-0.15) (p <0.05). The H-ras protein expressed in colon carcinomas co ntained activated form of H-ras without mutation, based on the findings obt ained by RBD-binding (ras binding domain of Raf protein) assay and PCR-SSCP analysis. In addition, we found that H-ras expression was higher in female patients than male, and in cancers with distant metastasis compared to tho se with non-distant metastasis. Good correlation between H-ras expression l evels and those of the upstream and downstream signaling proteins of EGFR, MEK and ERK was found, suggesting that H-ras may play a significant role in carcinogensis of colorectal cancer.