A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line

Niwa, Osami; Kumazaki, Tatsuo; Tsukiyama, Toshio; Soma, Gen‐Ichiro; Miyajima, Nobuyuki; Yokoro, Kenjiro

doi:10.1093/nar/18.22.6709

Cited by 19 publications

(21 citation statements)

References 2 publications

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“…Interestingly, alignment and detailed inspection of the amino acid sequence of the rat BCAT C from TZ103 cells with the previously identi®ed murine BCAT C (Niwa et al, 1990) and rat BCAT C (Hutson et al, 1996) revealed striking di erences at the Ntermini where our sequence was completely identical to the murine BCAT C (Niwa et al, 1990), whereas the sequence of rat BCAT C published by Hutson et al (1996) contained an N-terminal extension. Whether this To quantify the BCAT C RNA expression relative to GAPDH expression, the blot was reprobed with a 32 Plabeled GAPDH probe extension re¯ects a polymorphism or is due to an extra exon and whether it has any functional implications is so far not known.…”

Section: Discussionmentioning

confidence: 64%

“…One interesting candidate (clone 12) exhibited sequence identity to rat EST AA900881 and homology to a mouse mRNA that was shown to be overexpressed and ampli®ed in the teratocarcinoma cell line ECA39 (Niwa et al, 1990). The others were selected at random and included cDNA clone 16 with sequence identity to cytosolic protein tyrosine phosphatase RKPTP (Moriyama et al, 1994) and clone 2 with homology to mouse EST AA672232.…”

Section: Cloning Strategymentioning

confidence: 99%

“…Thus, assuming identical loading (deduced from Figure 3b) Figure 2 Multiple sequence alignment of eukaryotic branched chain aminotransferases (BCAT). The deduced amino acid sequence of rat BCAT C isolated from PNET cell line TZ103 (denoted TZ103 BCATc) (accession number AJ278701) was aligned with mouse ECA39 (murine BCAT C ; Niwa et al, 1990) (accession number X17502), the previously described rat BCAT C (Hutson et al, 1996), and the recently submitted sequence of rat BCATc from Kholodilov et al (2000) (accession number AF165887). The di erences in the rat sequences are highlighted the di erence in BCAT expression may be only ®vefold.…”

Section: Cloning Of a Full-length Cdna For Rat Est Aa900881mentioning

confidence: 99%

“…This view is supported by the following ®ndings. (1) The mouse homolog of this gene has previously been shown to be ampli®ed and overexpressed in a teratocarcinoma cell line (Niwa et al, 1990). (2) In an independent approach, this gene was isolated from c-myc induced mouse tumors and it has been demonstrated to be a direct target for c-myc activation (Benvenisty et al, 1992;Ben-Yosef et al, 1996).…”

Section: Significance Of the Amplified And Overexpressed Genes For Tumentioning

confidence: 99%

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Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

et al. 2001

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Primitive neuroectodermal tumors (PNETs) such as human medulloblastomas are genetically heterogeneous and therefore poorly understood. In a rat model the SV40 large T antigen was used to induce neoplasms with characteristic features of PNETs. Tumor development requires a latency period of 8 ± 11 months implicating secondary genetic alterations. To identify such secondary alterations we performed comparative analyses of two phenotypically identical PNET-derived cell lines. Indeed, these cell lines displayed distinct high-level ampli®cation sites. Using a combination of subtractive cDNA analysis and radiation hybrid mapping we have now identi®ed genes in the amplicon regions of the two cell lines. Interestingly, one of these genes encodes the rat homolog of a cytosolic branched chain aminotransferase (BCAT C ) previously shown to be ampli®ed in a mouse teratocarcinoma cell line. We propose that this simple cloning strategy may serve as a powerful tool for the isolation of genes implicated in known chromosomal aberrations in primary tumors and tumor cell lines. Oncogene (2001Oncogene ( ) 20, 2023Oncogene ( ± 2031

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Section: Discussionmentioning

confidence: 64%

Section: Cloning Strategymentioning

confidence: 99%

Section: Cloning Of a Full-length Cdna For Rat Est Aa900881mentioning

confidence: 99%

Section: Significance Of the Amplified And Overexpressed Genes For Tumentioning

confidence: 99%

See 2 more Smart Citations

Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

et al. 2001

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“…In the present study, we have demonstrated that the ECA39 expression, which can be suppressed by PSK, has the potential to predict distant metastasis. The ECA39 protein was originally identified by the overexpression of its mRNA in an undifferentiated mouse teratocarcinoma cell line [23] . The ECA39 gene harbors a functional c-Myc binding sequence located 3' of its transcription initiation site, and has been shown to be a direct target for c-Myc activity in both mice and humans [24,25] .…”

Section: Discussionmentioning

confidence: 99%

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

Yoshikawa

Yanagi²,

Shen³

et al. 2006

WJG

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AIM:To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC). METHODS: Firstly, we used protein microarrays toanalyze the in vitro expression profiles of potential PSKrelated markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients.RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05). CONCLUSION:Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

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Imaging of branched chain amino acid metabolism in tumors with hyperpolarized ¹³C ketoisocaproate

Karlsson¹,

Jensen²,

Zandt³

et al. 2010

Intl Journal of Cancer

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Powerful analytical tools are vital for characterizing the complex molecular changes underlying oncogenesis and cancer treatment. This is particularly true, if information is to be collected in vivo by noninvasive approaches. In the recent past, hyperpolarized 13 C magnetic resonance (MR) spectroscopy has been employed to quickly collect detailed spectral information on the chemical fate of tracer molecules in different tissues at high sensitivity. Here, we report a preclinical study showing that a-ketoisocaproic acid (KIC) can be used to assess molecular signatures of tumors with hyperpolarized MR spectroscopy. KIC is metabolized to leucine by the enzyme branched chain amino acid transferase (BCAT), which is found upregulated in some tumors. BCAT is a putative marker for metastasis and a target of the proto-oncogene c-myc. Very different fluxes through the BCAT-catalyzed reaction can be detected for murine lymphoma (EL4) and rat mammary adenocarcinoma (R3230AC) tumors in vivo. EL4 tumors show a more than 7-fold higher hyperpolarized 13 C leucine signal relative to the surrounding healthy tissue. In R3230AC tumor on the other hand branched chain amino acid metabolism is not enhanced relative to surrounding tissues. The distinct molecular signatures of branched chain amino acid metabolism in EL4 and R3230AC tumors correlate well with ex vivo assays of BCAT activity.Modern genetic tools have markedly improved the understanding of cancer as a genetic disease by linking the development, progression and remission of cancer to underlying genetic changes. 1,2 These approaches have also revealed the genetic heterogeneity of tumors. Thus, an understanding of the molecular signatures of the disease with noninvasive techniques would be highly desirable in order to define molecular targets for a tumor-specific or even personalized diagnosis and treatment.3 This can be achieved by hyperpolarized chemical shift imaging (CSI), which is a recently devised imaging modality for the visualization of molecular processes in vivo. [4][5][6] The method relies on a signal enhancement of the inherently weak nuclear magnetic resonance (NMR) signal by several orders of magnitude in a process termed dynamic nuclear polarization (DNP). This process increases the magnetization of nuclear spins ex situ to generate a 'hyperpolarized' molecule, which is injected as a nonradionuclide imaging marker. 7 The enhancement of detectable NMR signal by several orders of magnitude renders imaging experiments with a variety of substrates possible. As NMR is a high-resolution spectral technique, the method bears a unique potential to monitor chemical modifications of the hyperpolarized molecule in vivo. Previous studies using hyperpolarized pyruvate have detected cancer tissues by their increased anaerobic metabolism. 4,5,8 Notably, the method has also shown the potential to measure early tumor responses to therapy. 9 Cellular amino acid metabolism is regulated by the activity, organ distribution and cellular compartmentalization of metabolic enzymes incl...

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A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line

Cited by 19 publications

References 2 publications

Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

Imaging of branched chain amino acid metabolism in tumors with hyperpolarized ¹³C ketoisocaproate

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A cDNA clone overexpressed and amplified in a mouse teratocarcinoma line

Cited by 19 publications

References 2 publications

Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

Identification of amplified genes from SV40 large T antigen-induced rat PNET cell lines by subtractive cDNA analysis and radiation hybrid mapping

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

Imaging of branched chain amino acid metabolism in tumors with hyperpolarized 13C ketoisocaproate

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Imaging of branched chain amino acid metabolism in tumors with hyperpolarized ¹³C ketoisocaproate