Enhanced expression of p46 Shc in the nucleus and p52 Shc in the cytoplasm of human gastric cancer.
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.
Yukimasa
Satoko
S
Third Department of Internal Medicine, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Masaki
Tsutomu
T
Yoshida
Shuhei
S
Uchida
Naohito
N
Watanabe
Seishiro
S
Usuki
Hisashi
H
Yoshiji
Hitoshi
H
Maeta
Tsuyoshi
T
Ebara
Kazuo
K
Nakatsu
Toshiaki
T
Kurokohchi
Kazutaka
K
Kuriyama
Shigeki
S
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D015153:Blotting, Western; D002467:Cell Nucleus; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm; D005753:Gastric Mucosa; D006801:Humans; D007150:Immunohistochemistry; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1