Biomaterial Database

Malignant transformation by H-ras results in aberrant regulation of ribonucleotide reductase gene expression by transforming growth factor-beta 1. 1995

R A Hurta, and J A Wright

Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.

Ribonucleotide reductase is a key rate-limiting and regulatory step in DNA synthesis and plays a crucial role in the coordination of DNA synthesis, DNA repair, and cell proliferation. The present study demonstrates a link between alterations in TGF-beta 1 regulation during malignant conversion and the expression of ribonucleotide reductase. H-ras-transformed mouse 10T1/2 cell lines exhibiting malignant potential were examined for possible TGF-beta 1-mediated alterations in ribonucleotide reductase expression. Selective induction of ribonucleotide reductase gene expression occurred, since only H-ras-transformed highly metastatic cells exhibited marked elevations in ribonucleotide reductase expression, whereas nontransformed normal 10T1/2 cells were unaffected by TGF-beta 1 treatment. These changes occurred without any detectable modifications in DNA synthesis rates, suggesting that these changes were regulated by a novel mechanism independent of the S-phase of the cell cycle. Furthermore, this TGF-beta 1-mediated regulation of ribonucleotide reductase expression was shown to occur through an autocrine mechanism. TGF-beta 1-modulated regulation of ribonucleotide reductase expression requires de novo protein synthesis and involves, at least in part, transcriptional and post-transcriptional events. Furthermore, evidence is presented to suggest a possible role for protein kinase C-mediated events, protein phosphatases, and G-protein-coupled events in the TGF-beta 1-mediated regulation of ribonucleotide reductase expression in H-ras-transformed malignant cells. TGF-beta 1 regulation of ribonucleotide reductase in highly malignant cells appears to be complex and multifaceted and constitutes an integral part of an altered growth regulatory program.

UI	MeSH Term	Description	Entries
D011905	Genes, ras	Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.	Ha-ras Genes,Ki-ras Genes,N-ras Genes,c-Ha-ras Genes,c-Ki-ras Genes,c-N-ras Genes,ras Genes,v-Ha-ras Genes,v-Ki-ras Genes,H-ras Genes,H-ras Oncogenes,Ha-ras Oncogenes,K-ras Genes,K-ras Oncogenes,Ki-ras Oncogenes,N-ras Oncogenes,c-H-ras Genes,c-H-ras Proto-Oncogenes,c-Ha-ras Proto-Oncogenes,c-K-ras Genes,c-K-ras Proto-Oncogenes,c-Ki-ras Proto-Oncogenes,c-N-ras Proto-Oncogenes,ras Oncogene,v-H-ras Genes,v-H-ras Oncogenes,v-Ha-ras Oncogenes,v-K-ras Genes,v-K-ras Oncogenes,v-Ki-ras Oncogenes,Gene, Ha-ras,Gene, Ki-ras,Gene, v-Ha-ras,Gene, v-Ki-ras,Genes, Ha-ras,Genes, Ki-ras,Genes, N-ras,Genes, v-Ha-ras,Genes, v-Ki-ras,H ras Genes,H ras Oncogenes,H-ras Gene,H-ras Oncogene,Ha ras Genes,Ha ras Oncogenes,Ha-ras Gene,Ha-ras Oncogene,K ras Genes,K ras Oncogenes,K-ras Gene,K-ras Oncogene,Ki ras Genes,Ki ras Oncogenes,Ki-ras Gene,Ki-ras Oncogene,N ras Genes,N ras Oncogenes,N-ras Gene,N-ras Oncogene,c H ras Genes,c H ras Proto Oncogenes,c Ha ras Genes,c Ha ras Proto Oncogenes,c K ras Genes,c K ras Proto Oncogenes,c Ki ras Genes,c Ki ras Proto Oncogenes,c N ras Genes,c N ras Proto Oncogenes,c-H-ras Gene,c-H-ras Proto-Oncogene,c-Ha-ras Gene,c-Ha-ras Proto-Oncogene,c-K-ras Gene,c-K-ras Proto-Oncogene,c-Ki-ras Gene,c-Ki-ras Proto-Oncogene,c-N-ras Gene,c-N-ras Proto-Oncogene,ras Gene,ras Oncogenes,v H ras Genes,v H ras Oncogenes,v Ha ras Genes,v Ha ras Oncogenes,v K ras Genes,v K ras Oncogenes,v Ki ras Genes,v Ki ras Oncogenes,v-H-ras Gene,v-H-ras Oncogene,v-Ha-ras Gene,v-Ha-ras Oncogene,v-K-ras Gene,v-K-ras Oncogene,v-Ki-ras Gene,v-Ki-ras Oncogene
D002461	Cell Line, Transformed	Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.	Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002471	Cell Transformation, Neoplastic	Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.	Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D005354	Fibrosarcoma	A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)	Fibrosarcomas
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012264	Ribonucleotide Reductases		Ribonucleotide Reductase,Reductase, Ribonucleotide,Reductases, Ribonucleotide
D014162	Transfection	The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.	Transfections
D015971	Gene Expression Regulation, Enzymologic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.	Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D015972	Gene Expression Regulation, Neoplastic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.	Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D016196	S Phase	Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.	S Period,Period, S,Periods, S,Phase, S,Phases, S,S Periods,S Phases