Involvement of G‐patch domain containing 2 overexpression in breast carcinogenesis

Lin, Mo‐Jun; Fukukawa, Chikako; Park, Jae-Hyun; Naito, Kie; Kijima, Kyoko; Shimo, Arata; Ajiro, Masahiko; Nishidate, Toshihiko; Nakamura, Yusuke; Katagiri, Toyomasa

doi:10.1111/j.1349-7006.2009.01185.x

Cited by 45 publications

(58 citation statements)

References 24 publications

(49 reference statements)

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“…GPAT2 silencing also diminished cell proliferation of HCT116 cells and both murine and human GPAT2 overexpression increased cell proliferation. These results agree with experiments reporting either siRNA-mediated silencing or overexpression of specific CT genes, which demonstrate causality between CT gene expression and growth phenotype [21]–[25]. The dramatic reduction of the MDA-MB-231 tumor phenotype by GPAT2 silencing was also evident in vivo , because knocked down cells were unable to generate tumor xenografts in nude mice.…”

Section: Discussionsupporting

confidence: 90%

Glycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene and Promotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 Cell Line

et al. 2014

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The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics approach, we found that GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, and we validated GPAT2 expression at the protein level in breast cancer by immunohistochemistry. In this case GPAT2 expression correlated with a higher histological grade. 5-Aza-2′ deoxycytidine treatment of human cells lines induced GPAT2 expression suggesting epigenetic regulation of gene expression. In order to evaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expression in MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorage independent growth, migration and tumorigenicity, and increased staurosporine-induced apoptosis. In contrast, GPAT2 over-expression increased cell proliferation rate and resistance to staurosporine-induced apoptosis. To understand the functional role of GPAT2, we performed a co-expression analysis in mouse and human testis and found a significant association with semantic terms involved in cell cycle, DNA integrity maintenance, piRNA biogenesis and epigenetic regulation. Overall, these results indicate the GPAT2 would be directly associated with the control of cell proliferation. In conclusion, we confirm GPAT2 as a cancer testis gene and that its expression contributes to the tumor phenotype of MDA-MB-231 cells.

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Section: Discussionsupporting

confidence: 90%

Glycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene and Promotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 Cell Line

et al. 2014

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“…Through the genome-wide expression analysis of a large number of microdissected clinical cancer materials, we have identified dozens of genes that function as oncogenes in the process of development and/or progression of breast cancer (10)(11)(12)(13)(14)(15)(16)(17), bladder cancer (18,19), synovial sarcoma (20,21), testicular seminoma (22), and renal cell carcinoma (23,24). Such molecules are considered to be candidate molecular targets for development of new therapeutic modalities.…”

Section: Introductionmentioning

confidence: 99%

Involvement of C12orf32 overexpression in breast carcinogenesis

Kim

Fukukawa²,

Ueda³

et al. 2010

Int J Oncol

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Abstract. Through genome-wide gene expression profile analysis of breast cancer, we identified a gene, chromosome 12 open reading frame 32 (C12orf32), to be involved in mammary carcinogenesis. Semiquantitative RT-PCR and Northern blot analysis confirmed C12orf32 overexpression in breast cancer cells and its almost undetectable level of expression in normal human tissues. Immunocytochemical staining analysis using breast cancer cell lines revealed a cell cycle-dependent subcellular localization of endogenous C12orf32 protein. Depletion of C12orf32 expression by small-hairpin RNA interference significantly suppressed the growth of breast cancer cell lines possibly due to the inhibition of G1/S transition and subsequent cell death. Western blot analysis indicated that a C12orf32 protein of 35 kDa predicted from the cDNA sequences was processed to a 16-kDa protein of (C12orf32-p16) which was accumulated in most of breast cancer cell lines examined. Our data suggest that C12orf32 is a promising molecular target for the development of novel anticancer drugs such as peptide vaccines and siRNA drugs.

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“…Hence, development of novel moleculartargeted drugs for breast cancer with higher efficacy and low risk of adverse reactions is essentially important to improve clinical management. Toward development of such therapeutic agents, we had analyzed the genome-wide gene expression profile of 81 breast cancers as well as 29 normal human organs using cDNA microarray and have reported several novel target candidates for breast cancer therapy (3)(4)(5)(6)(7)(8)(9)(10)(11). In this article, we describe the identification and characterization of UDP-N-acetyl-α-D-galactosamine (GalNAc):polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which was upregulated in a great majority of breast cancer cases.…”

Section: Introductionmentioning

confidence: 99%

Critical Roles of Mucin 1 Glycosylation by Transactivated PolypeptideN-Acetylgalactosaminyltransferase 6 in Mammary Carcinogenesis

et al. 2010

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The structure of O-glycosylated proteins is altered in breast cancer cells, but the mechanisms of such an aberrant modification have been largely unknown. We here report critical roles of a novel druggable target, polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which is upregulated in a great majority of breast cancers and encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation. Knockdown of GALNT6 by small interfering RNA significantly enhanced cell adhesion function and suppressed the growth of breast cancer cells. Western blot and immunostaining analyses indicated that wild-type GALNT6 protein could glycosylate and stabilize an oncoprotein mucin 1 (MUC1), which was upregulated with GALNT6 in breast cancer specimens. Furthermore, knockdown of GALNT6 or MUC1 led to similar morphologic changes of cancer cells accompanied by the increase of cell adhesion molecules β-catenin and E-cadherin. Our findings implied that overexpression of GALNT6 might contribute to mammary carcinogenesis through aberrant glycosylation and stabilization of MUC1 and that screening of GALNT6 inhibitors would be valuable for the development of novel therapeutic modalities against breast cancer. Cancer Res; 70(7); 2759-69. ©2010 AACR.

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Involvement of G‐patch domain containing 2 overexpression in breast carcinogenesis

Cited by 45 publications

References 24 publications

Glycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene and Promotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 Cell Line

Glycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene and Promotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 Cell Line

Involvement of C12orf32 overexpression in breast carcinogenesis

Critical Roles of Mucin 1 Glycosylation by Transactivated PolypeptideN-Acetylgalactosaminyltransferase 6 in Mammary Carcinogenesis

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