Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC

Hosoi, Yoshio; Kapp, Leon N.; Murnane, John P.; Matsumoto, Yoshihisa; Enomoto, Atsushi; Ono, Tetsuya; Miyagawa, Kiyoshi

doi:10.1016/j.bbrc.2006.07.115

Cited by 17 publications

(18 citation statements)

References 18 publications

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“…We observed that TRIM29 was only detected in the tumor lines SK-BR-3, MDA-MB-468, and non-tumorigenic mammary epithelium-derived MCF-10A and immortalized human mammary epithelium cells (HMEC) by immunoblotting (Fig 1A), consistent with a previous study (23). Further, when relative TRIM29 mRNA was quantified by qRT-PCR, transcript was only detectable in these four cell lines (Fig 1B).…”

Section: Resultssupporting

confidence: 92%

TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior

Kim

Alpay

et al. 2014

Cancer Research

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TRIM29 (ATDC) exhibits a contextual function in cancer, but appears to exert a tumor suppressor role in breast cancer. Here we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival (RFS), increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT.

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Section: Resultssupporting

confidence: 92%

TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior

Kim

Alpay

et al. 2014

Cancer Research

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“…Also, at least in one study, suppressed ATDC expression has been shown to associate with malignant phenotypes in some cancer cells (20). Further work will be required to clarify how ATDC might function in opposing pathways and to completely understand how ATDC contributes to changes in tumor cell growth and metastasis.…”

Section: Discussionmentioning

confidence: 98%

The ATDC (TRIM29) Protein Binds p53 and Antagonizes p53-Mediated Functions

Yuan

Villagra

Peng

et al. 2010

Molecular and Cellular Biology

101

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The ataxia telangiectasia group D-complementing (ATDC) gene product, also known as TRIM29, is a member of the tripartite motif (TRIM) protein family. ATDC has been proposed to form homo-or heterodimers and to bind nucleic acids. In cell cultures, ATDC expression leads to rapid growth and resistance to ionizing radiation (IR), whereas silencing of ATDC expression decreases growth rates and increases sensitivity to IR. Although ATDC is overexpressed in many human cancers, the biological significance of ATDC overexpression remains obscure. We report here that ATDC increases cell proliferation via inhibition of p53 nuclear activities. ATDC represses the expression of p53-regulated genes, including p21 and NOXA. Mechanistically, ATDC binds p53, and this interaction is potentially fine-tuned by posttranslational acetylation of lysine 116 on ATDC. The association of p53 and ATDC results in p53 sequestration outside of the nucleus. Together, these results provide novel mechanistic insights into the function of ATDC and offer an explanation for how ATDC promotes cancer cell proliferation.Ataxia telangiectasia (AT) is an autosomal-recessive, complex, multisystem disorder (4, 33). One of the hallmarks for cells derived from AT patients is their unusual sensitivity to ionizing radiation (IR) and their failure to delay the cell cycle in S phase, termed radioresistant DNA synthesis. In addition, AT cells contain atypical cytoskeletal organization. An early attempt to complement the defect in an AT cell line (AT5BIVA) by transfection with a human cosmid library and selection by ␥IR resulted in the isolation of an AT cell line (1B3) that was partially resistant to IR (22). Subsequent isolation of the human DNA in the region of the integrated cosmid sequences in 1B3 cells resulted in the cloning of the ataxia telangiectasia group D-complementing (ATDC) gene (23).The ATDC gene is located at chromosome 11q23, where it is frequently associated with many different kinds of cancers. Analysis of the ATDC gene product revealed that it is a member of the tripartite motif (TRIM) protein family (also known as the RBCC family). This protein family is characterized by three zinc-binding domains, a RING, a B-box type 1, and a B-box type 2, followed by a coiled-coil region (5,29,42,43,47). Some TRIM proteins homo-multimerize through their coilcoil region, and the integrity of the TRIM motif is required for proper subcellular localization of TRIM proteins (43). Recently, it was discovered that one of the TRIM proteins is a component of the repressor binding site (RBS) binding complex found in EC and ES cells and functions in restricting retroviral replication (60).The ATDC protein has been shown to interact with a protein kinase C substrate and inhibitor, although the significance of this interaction is not exactly clear (6). Although early studies indicate that ATDC can complement the IR sensitivity of AT fibroblasts, later analysis reveals that ATDC does not affect radioresistant DNA synthesis and is most likely not mutated in any AT patient...

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“…The inoculated plates were incubated for 7 days and stained with cell stain solution according to the manufacturer's instruction. The number of colonies was determined using BioImaging systems (UVP, LabworksTM, Ver 4.6) (Bennett et al 2007;Hosoi et al 2006).…”

Section: Soft-agar Colony Forming Assaymentioning

confidence: 99%

Growth Inhibitory Effect of the Ternary Complex Factor Net on Human Pancreatic Carcinoma Cell Lines

Zhu

et al. 2008

Tohoku J. Exp. Med.

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Pancreatic carcinoma is one of the most aggressive malignancies and carries the most dismal prognoses of all cancers. A better understanding of the genes involving in tumor development may allow us to tackle this rapidly progressive disease. The Net gene belongs to the ternary complex transcription factor (TCF) family and is regulated by the Ras/mitogen-activited protein kinase-signaling pathway. Under basal conditions, Net shows strong represssing function on transcription of proto-oncogene gene c-fos. Moreover, the lower expression of Net has been noted in some carcinoma cells, such as cervical cancer. To study the effect of Net on c-fos expression and its potential role in the growth of pancreatic carcinoma, we developed a recombinant plasmid, a pEGFP-N1-Net, which codes for Net-EGFP fusion proteins, and stably transfected it into BxPC-3 human pancreatic carcinoma cells. Using stable transformants, we were able to show that overexpression of Net decreased the expression of c-fos and inhibited pancreatic cancer cell proliferation. Cell cycle analysis demonstrated that Net overexpression inhibited cell cycle progression. These findings suggested that loss of Net repression could augment c-fos expression and further trigger neoplastic cell proliferation, which was involved in the pathogenesis of pancreatic cancer. Therefore, Net might be a potential target for the treatment of c-fos-positive pancreatic cancer.

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Suppression of anchorage-independent growth by expression of the ataxia-telangiectasia group D complementing gene, ATDC

Cited by 17 publications

References 18 publications

TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior

TRIM29 Suppresses TWIST1 and Invasive Breast Cancer Behavior

The ATDC (TRIM29) Protein Binds p53 and Antagonizes p53-Mediated Functions

Growth Inhibitory Effect of the Ternary Complex Factor Net on Human Pancreatic Carcinoma Cell Lines

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