Increased level of the mitochondrial ND5 transcript in chemically induced rat hepatomas

Corral, Marisol; Paris, Brigitte; Baffet, Georges; Tichonicky, Lydie; Guguen‐Guillouzo, Christiane; Kruh, Jacques; Defer, Nicole

doi:10.1016/0014-4827(89)90374-1

Cited by 41 publications

(19 citation statements)

References 36 publications

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“…This site could thus easily function as an enhancer element for both promoters and, following HMGA1 binding, increase transcription from both the heavy and light DNA strands, consistent with the present observations. Interestingly, in this connection, there are many examples of up-regulated heavy chain gene expression in different cancer types [15,16,25] and ND2 is especially significant since it has been reported to be specifically activated in malignant tissue as compared to normal tissue taken from the same colorectal cancer patients [26]. Taken together, the current data and published results support the possibility that HMGA1 proteins may serve a dual organelle function whereby binding to a single site in the D-loop influences the regulation of not only transcription but also replication of mtDNA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Nuclear HMGA1 nonhistone chromatin proteins directly influence mitochondrial transcription, maintenance, and function

Dement

Maloney

Reeves

2007

Experimental Cell Research

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We have previously demonstrated that HMGA1 proteins translocate from the nucleus to mitochondria and bind to mitochondrial DNA (mtDNA) at the D-loop control region [11]. To elucidate possible physiological roles for such binding, we employed methods to analyze mtDNA transcription, mitochondrial maintenance and other organelle functions in transgenic human MCF-7 cells (HA7C) induced to over-express an HA-tagged HMGA1 protein and control (parental) MCF-7 cells. Quantitative real-time (RT) PCR analyses demonstrated that mtDNA levels were reduced approximately 2-fold in HMGA1 over-expressing HA7C cells and flow cytometric analyses further revealed that mitochondrial mass was significantly reduced in these cells. Cellular ATP levels were also reduced in HA7C cells and survival studies showed an increased sensitivity to killing by 2-deoxy-D-glucose, a glycolysis-specific inhibitor. Flow cytometric analyses revealed additional mitochondrial abnormalities in HA7C cells that are consistent with a cancerous phenotype: namely, increased reactive oxygen species (ROS) and increased mitochondrial membrane potential (Δψ m ). Additional RT-PCR analyses demonstrated that gene transcripts from both the heavy (ND2, COXI, ATP6) and light (ND6) strands of mtDNA were up-regulated approximately 3-fold in HA7C cells. Together, these mitochondrial changes are consistent with many previous reports and reveal several possible mechanisms by which HMGA1 over-expression, a common feature of naturally occurring cancers, may affect tumor progression.

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Section: Discussionmentioning

confidence: 99%

Nuclear HMGA1 nonhistone chromatin proteins directly influence mitochondrial transcription, maintenance, and function

Dement

Maloney

Reeves

2007

Experimental Cell Research

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“…Several distinct differences between the mitochondria of cancer cells and normal cells have already been observed at the genetic, molecular and biochemical levels and these studies have indicated that mitochondrial dysfunction is involved in carcinogenesis. In particular, activation of the genes for COXI, COXII, and 16S rRNA was shown in rat fibroblast cells immortalized or transformed by viral and cellular oncogenes [14]; ND5, ND6, cytochrome b, COXII, and 16S rRNA in chemically induced rat hepatomas [15]; ND1, 12S rRNA, and 16S rRNA in polyps of familial polyposis coli patients [16]. Elevated levels of ATP6, ND5, cytochrome b, COXI, and COXII mRNAs were revealed in papillary thyroid carcinomas as compared to normal thyroid tissue [17].…”

Section: Discussionmentioning

confidence: 99%

“…Differential hybridization of one such plasmid DNA blot is shown in Fig. 1 where is possible to see that some cDNA inserts (lanes 10, 26) hybridized more intensive with a GB cDNA probe while the majority (lanes 1,5,9,15,16,19,24,25,28) hybridized more intensive with the normal adult human brain cDNA probe.…”

Section: Identification Of Genes With Altered Expression In Gbs By DImentioning

confidence: 99%

Reduction of the transcription level of the mitochondrial genome in human glioblastoma

et al. 2005

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Screening of human fetal brain cDNA library by glioblastoma (GB) and normal human brain total cDNA probes revealed 80 differentially hybridized clones. Hybridization of the DNA from selected clones and the same cDNA probes confirmed this difference for 38 clones, of which eight clones contained Alu-repeat inserts with increased levels in GB. Thirty clones contained cDNAs corresponding to mitochondrial genes for ATP synthase subunit 6 (ATP6), cytochrome c oxidase subunit II (COXII), cytochrome c oxidase subunit III (COXIII), NADH dehydrogenase subunit 1 (ND1), NADH dehydrogenase subunit 4 (ND4), and mitochondrial 12S rRNA. The levels of all these mitochondrial transcripts were decreased in glioblastomas as compared to tumor-adjacent histologically normal brain. Earlier we found the same for cytochrome c oxidase subunit I (COXI) Serial Analysis of Gene Expression (SAGE) showed lower content of the tags for all mitochondrial genes in GB SAGE libraries and together with our experimental data could serve as evidence of general inactivation of the mitochondrial genome in glioblastoma-the most malignant and abundant form of human brain tumor. q 2004 Published by Elsevier Ireland Ltd.

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“…Burgart et al (1995) detected somatic mutations (50 bp) in the D-loop region of gastric carcinoma. Increase in mtDNA encoded transcripts for ND5, cytochrome c oxidase II and 16S r RNA were also observed in chemically induced rat hepatomas (Corral 1989). Almost every type of solid tumor is associated with mtDNA mutations as summarized in Table 1.…”

Section: Solid Tumorsmentioning

confidence: 80%

Cancer — the mitochondrial connection

Paul

Mukhopadhyay

2007

Biologia

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Mitochondria are the powerhouse of the cell. They play a vital role in the energy metabolism and regulate calcium flux and apoptosis. The recent resurgence of interest in mitochondrial studies is largely attributed to the recognition that mitochondrial dysfunctions lead to various physiopathological disorders, especially in the development and progression of cancer. Mitochondrial DNA is very susceptible to mutations, which lead to respiratory dysfunction and are implicated in many cancers. Mitochondria serve as the molecular target for a structurally diverse group of pharmacological agents in cancer chemotherapy. Biochemical and biophysical characterization have helped to identify several important differences between mitochondria of normal and disease state. Such unique alterations in mitochondrial structure and function could become promising target for the development of new generation drugs.

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Increased level of the mitochondrial ND5 transcript in chemically induced rat hepatomas

Cited by 41 publications

References 36 publications

Nuclear HMGA1 nonhistone chromatin proteins directly influence mitochondrial transcription, maintenance, and function

Nuclear HMGA1 nonhistone chromatin proteins directly influence mitochondrial transcription, maintenance, and function

Reduction of the transcription level of the mitochondrial genome in human glioblastoma

Cancer — the mitochondrial connection

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