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Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer
Author(s) -
Oki Eiji,
Baba Hideo,
Tokunaga Eriko,
Nakamura Toshihiko,
Ueda Naoyuki,
Futatsugi Motonori,
Mashino Kohjiro,
Yamamoto Manabu,
Ikebe Masahiko,
Kakeji Yoshihiro,
Maehara Yoshihiko
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21170
Subject(s) - pten , protein kinase b , cancer , cancer research , pi3k/akt/mtor pathway , medicine , phosphorylation , oncology , biology , signal transduction , biochemistry
Growth factor receptor‐mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. We describe a pathway that involves AKT/PI3K to mediate chemoresistance in gastric cancer patients. Primary gastric carcinoma tissues and corresponding normal mucosa were obtained from 76 gastric cancer patients who underwent surgery in the Department of Surgery II in Kyushu University Hospital from the years 1996–2000. AKT activation was investigated by immunostaining with a phosphorylation‐specific antibody, and LOH (loss of heterozygosity) of PTEN was studied in the same samples. AKT was phosphorylated in 22 cases (28.9%) of gastric cancer cases. AKT and phosphorylated AKT were not correlated with any clinicopathological factor. We found that the gastric cancer patients who had higher AKT phosphorylation (activated AKT) seemed to have LOH of PTEN ( p = 0.0008). When the chemotherapeutic sensibilities of these patients were studied in an MTT assay, it was found that the activated AKT was associated with increased resistance to multiple chemotherapeutic agents (5‐fluorouracil, adriamycin, mitomycin C and cis‐platinum). The results of our study indicate that AKT activation and LOH of PTEN plays an important role in conferring a broad‐spectrum chemoresistance in gastric cancer patients. It also indicates that AKT may therefore be a novel molecular target for therapies or chemosensitivity tests that improve the outcomes of gastric cancer patients. © 2005 Wiley‐Liss, Inc.