Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression

Yu Nakamura; Toshiro Migita; Fumie Hosoda; Naoko Okada; Masahiro Gotoh; Yasuhito Arai; Michiyo Fukushima; Misao Ohki; Satoshi Miyata; Kengo Takeuchi; Issei Imoto; Hitoshi Katai; Toshiharu Yamaguchi; Johji Inazawa; Setsuo Hirohashi; Yuichi Ishikawa; Tatsuhiro Shibata

doi:10.1002/ijc.24538

Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression

Yu Nakamura, Toshiro Migita, Fumie Hosoda, Naoko Okada, Masahiro Gotoh, Yasuhito Arai, Michiyo Fukushima, Misao Ohki, Satoshi Miyata, Kengo Takeuchi, Issei Imoto, Hitoshi Katai, Toshiharu Yamaguchi, Johji Inazawa, Setsuo Hirohashi, Yuichi Ishikawa, Tatsuhiro Shibata

Medicine

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

Abstract

Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identi-fied, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Kr€uppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a signifi-cant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures.

Original language	English
Pages (from-to)	1859-1867
Number of pages	9
Journal	International Journal of Cancer
Volume	125
Issue number	8
DOIs	https://doi.org/10.1002/ijc.24538
Publication status	Published - 2009 Oct 15

Keywords

Gastric cancer
KLF12
Oncogene

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ijc.24538

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Nakamura, Y., Migita, T., Hosoda, F., Okada, N., Gotoh, M., Arai, Y., Fukushima, M., Ohki, M., Miyata, S., Takeuchi, K., Imoto, I., Katai, H., Yamaguchi, T., Inazawa, J., Hirohashi, S., Ishikawa, Y., & Shibata, T. (2009). Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. International Journal of Cancer, 125(8), 1859-1867. https://doi.org/10.1002/ijc.24538

Nakamura, Y, Migita, T, Hosoda, F, Okada, N, Gotoh, M, Arai, Y, Fukushima, M, Ohki, M, Miyata, S, Takeuchi, K, Imoto, I, Katai, H, Yamaguchi, T, Inazawa, J, Hirohashi, S, Ishikawa, Y & Shibata, T 2009, 'Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression', International Journal of Cancer, vol. 125, no. 8, pp. 1859-1867. https://doi.org/10.1002/ijc.24538

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abstract = "Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identi-fied, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Kr€uppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a signifi-cant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures.",

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AU - Gotoh, Masahiro

AU - Arai, Yasuhito

AU - Fukushima, Michiyo

AU - Ohki, Misao

AU - Miyata, Satoshi

AU - Takeuchi, Kengo

AU - Imoto, Issei

AU - Katai, Hitoshi

AU - Yamaguchi, Toshiharu

AU - Inazawa, Johji

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AB - Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identi-fied, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Kr€uppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a signifi-cant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures.

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Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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