AKT phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer

Eiji Oki, Hideo Baba, Eriko Tokunaga, Toshihiko Nakamura, Naoyuki Ueda, Motonori Futatsugi, Kohjiro Mashino, Manabu Yamamoto, Masahiko Ikebe, Yoshihiro Kakeji, Yoshihiko Maehara

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158 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)376-380
Number of pages5
JournalInternational Journal of Cancer
Volume117
Issue number3
DOIs
Publication statusPublished - Nov 10 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Oki, E., Baba, H., Tokunaga, E., Nakamura, T., Ueda, N., Futatsugi, M., Mashino, K., Yamamoto, M., Ikebe, M., Kakeji, Y., & Maehara, Y. (2005). AKT phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. International Journal of Cancer, 117(3), 376-380. https://doi.org/10.1002/ijc.21170