Up-regulation of cytoskeletal-associated protein 2 in primary human gastric adenocarcinomas

原发性人类胃腺癌中细胞骨架相关蛋白2的表达上调

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Abstract

BACKGROUND AND METHOD: We performed differential-display polymerase chain reaction to find up-regulated sequences in primary human gastric cancers, and cloned one up-regulated sequence, which was expressed in all the gastric cancer cells that we examined. The cloned sequence was identified as cytoskeletal-associated protein 2 (CKAP2). We also cloned a shorter splice variant, CKAP2-s. The CKAP2 or CKAP2-s protein in HeLa cells was localized to microtubule organizing centers (MTOC) and microtubules. This co-localization pattern was disrupted by nocodazole, a microtubule-destabilizing agent. RESULTS: These observations suggested that CKAP2 might be associated with microtubule networks. CKAP2 protein was detected in neither normal GI tract nor normal gastric mucosa. However, both CKAP2 and CKAP2-s mRNAs were up-regulated in 55% (23 out of 42 samples) of primary human gastric cancers by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, CKAP2 proteins were detected in immunohistochemical staining in all the gastric cancer samples that we examined. CKAP2 protein-expressing cells were also found in gastric adenomas. The average number of CKAP2 protein-positive cells in adenocarcinomas was 48.8%, which was significantly higher than the number in tubular adenomas, 9.1%. CONCLUSION: When these points were taken together, we concluded that CKAP2 is up-regulated in primary human gastric adenocarcinomas at high frequency and might be useful for diagnosing and discriminating adenocarcinomas from tubular adenomas of the stomach.

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