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Pathophysiological role of the activation of p38 mitogen‐activated protein kinases in poorly differentiated gastric cancer
Author(s) -
Atsumi Tomoaki,
Kato Katsuaki,
Uno Kaname,
Iijima Katsunori,
Koike Tomoyuki,
Imatani Akira,
Ohara Syuichi,
Shimosegawa Tooru
Publication year - 2007
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2007.02152.x
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , kinase , cancer , cancer cell , cancer research , microbiology and biotechnology , cell , protein kinase a , immunohistochemistry , biology , pathology , chemistry , medicine , biochemistry
p38 mitogen‐activated protein kinases (MAPK) contribute to the loss of cell–cell contact and the round cell shape characteristic of poorly differentiated gastric cancer. In the present study it is demonstrated that phospho‐p38 MAPK level significantly increased in poorly differentiated gastric cancers in comparison to differentiated cancers and normal gastric mucosa by immunohistochemistry. Next, the pathophysiological roles of p38 MAPK activation were investigated in differentiated gastric cancer cell lines MKN7 and MKN28 and poorly differentiated gastric cancer cell lines KATO‐III and MKN45 cells by incubating with specific p38 inhibitor SB203580 or inactivating analog SB202474. The distribution of F‐actin on phalloidin staining was identified as fine cytoskeletal filaments in MKN7 and MKN28, but as dense membranous accumulation in KATO‐III and MKN45 cells. The treatment with SB203580 but not SB202474 reduced irregular accumulation of F‐actin in KATO‐III and MKN45 cells. The expression of E‐cadherin, ZO‐1, occludin and claudin 4 was higher in MKN7 and MKN28 than KATO‐III and MKN45 cells. The expression of E‐cadherin in KATO‐III cells was increased following treatment with SB203580, suggesting the suppression of E‐cadherin at the transcriptional level independent of its genetic alterations. Thus, p38 MAPK signaling might contribute to the acquisition of malignant properties in poorly differentiated phenotypes.