Shc protein is known to be related to cell proliferation and carcinogenesis. However, the involvement of Shc in gastric cancer remains unknown. In the present study, we examined the expression and localization of Shc in human gastric cancer and the adjacent normal mucosa by Western blotting and immunohistochemical analyses. Furthermore, the expression of Shc in a gastric cancer cell line, MKN 28, was also studied. p66 Shc was not detected at all in gastric cancer or the adjacent normal mucosa. In contrast, immunohistochemical and Western blot analyses revealed that p52 Shc was detected in the cytoplasmic fractions obtained from gastric normal mucosa and cancer, while p46 Shc expression was observed in the nuclear fractions from gastric normal mucosa and cancer. Furthermore, not only p52 Shc expression in the cytoplasm but also p46 Shc expression in the nucleus was much higher in gastric cancer than in the adjacent normal mucosa. Subsequent in vitro experiments with MKN 28 gastric cancer cells also revealed that p52 Shc was expressed solely in the cytoplasm and p46 Shc was solely in the nucleus. These results suggest that the enhancement of p46 Shc and p52 Shc expression may be related to the occurrence of gastric cancer. Furthermore, unlike p52 Shc, p46 Shc was shown to be expressed solely in the nucleus, suggesting that p46 Shc expressed in the nucleus may play an important role in gastric carcinogenesis.

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