DOI: 10.1158/0008-5472.can-04-1543. <b> <i>Lysyl Oxidase</i> </b> Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers

Lysyl Oxidase Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers

10.1158/0008-5472.can-04-1543

Crossref journal-article

American Association for Cancer Research (AACR)

Cancer Research (1086)

Abstract

Abstract Lysyl oxidase (LOX) and HRAS-like suppressor (HRASLS) are silenced in human gastric cancers and are reported to have growth-suppressive activities in ras-transformed mouse/rat fibroblasts. Here, we analyzed whether or not LOX and HRASLS are tumor suppressor genes in human gastric cancers. Loss of heterozygosity and promoter methylation of LOX were detected in 33% (9 of 27) and 27% (26 of 96) of gastric cancers, respectively. Biallelic methylation and loss of heterozygosity with promoter methylation were also demonstrated in gastric cancers. Silencing of LOX was also observed in colon, lung, and ovarian cancer cell lines. As for mutations, only one possible somatic mutation was found by analysis of 96 gastric cancer samples and 58 gastric and other cancer cell lines. When LOX was introduced into a gastric cancer cell line, MKN28, in which LOX and HRASLS were silenced, it reduced the number of anchorage-dependent colonies to 57 to 61%, and the number of anchorage-independent colonies to 11 to 23%. Sizes of tumors formed in nude mice were reduced to 19 to 26%. Growth suppression in soft agar assay was also observed in another gastric cancer cell line, KATOIII. On the other hand, neither loss of heterozygosity nor a somatic mutation was detected in HRASLS, and its introduction into MKN28 did not suppress the growth in vitro or in vivo. These data showed that LOX is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in gastric cancers, and possibly also in other cancers.

Bibliography

Kaneda, A., Wakazono, K., Tsukamoto, T., Watanabe, N., Yagi, Y., Tatematsu, M., Kaminishi, M., Sugimura, T., & Ushijima, T. (2004). Lysyl Oxidase Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers. Cancer Research, 64(18), 6410â6415.

Authors 9

Atsushi Kaneda (first)
Kuniko Wakazono (additional)
Tetsuya Tsukamoto (additional)
Naoko Watanabe (additional)
Yukiko Yagi (additional)
Masae Tatematsu (additional)
Michio Kaminishi (additional)
Takashi Sugimura (additional)
Toshikazu Ushijima (additional)

References 43 Referenced 134

Dates

Type	When
Created	19 years, 11 months ago (Sept. 20, 2005, 6:43 p.m.)
Deposited	2 years, 7 months ago (Jan. 11, 2023, 4 p.m.)
Indexed	1 week, 1 day ago (Aug. 29, 2025, 5:53 a.m.)
Issued	20 years, 11 months ago (Sept. 15, 2004)
Published	20 years, 11 months ago (Sept. 15, 2004)
Published Online	20 years, 11 months ago (Sept. 16, 2004)
Published Print	20 years, 11 months ago (Sept. 15, 2004)

Funders 0

None

BibTeX

@article{Kaneda_2004, title={ Lysyl Oxidase Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers}, volume={64}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-04-1543}, DOI={10.1158/0008-5472.can-04-1543}, number={18}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Kaneda, Atsushi and Wakazono, Kuniko and Tsukamoto, Tetsuya and Watanabe, Naoko and Yagi, Yukiko and Tatematsu, Masae and Kaminishi, Michio and Sugimura, Takashi and Ushijima, Toshikazu}, year={2004}, month=sep, pages={6410–6415} }

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