Homeobox genes: potential candidates for the transcriptional control of the transformed and invasive phenotype. 1994

V Castronovo, and M Kusaka, and A Chariot, and J Gielen, and M Sobel
Metastasis Research Laboratory, University of Liège, Belgium.

The transformation of a cell and the acquisition of the invasive and metastatic phenotype result from the activation of a group of complex cellular processes rather than from the effect of a single gene product. It is likely that the coordination of the multiple genes involved in malignancy is under the control of a few genes that act as master genes or orchestrator genes. The latter probably code for transcription factors that control the genetic program for tumor invasion and metastasis. Homeobox genes are a family of transcription factors that contain a 183 bp highly conserved nucleotide sequence coding for a 61 amino acid domain that binds specifically to DNA. First discovered in Drosophila as genes controlling segmentation and segment identity, homeobox genes have since been identified in many other species including nematodes, frog, mouse and human. There is strong support for the suggestion that homeobox genes play a key role in development and differentiation. In humans, there are 38 homeobox genes organized in four clusters that are localized on chromosomes 2, 7, 12 and 17. The specific functions of each of these genes are generally unknown. Alterations in expression of several homeobox genes have been reported in a variety of malignant lesions, suggesting that they could play a role in the development of cancer. Using reverse transcriptase reaction coupled with polymerase chain reaction and degenerate oligonucleotides corresponding to the 5' and 3' ends of the highly conserved homeodomain, we amplified 130 bp cDNA fragments from the human breast cancer cell line MCF7 that were subsequently cloned into pBluescript vector. Sequencing of the clones, resulted in the identification of the homeodomains of four different human homeobox genes: HOXB6, HOXA1, HOXA10 and HOXC6. Further studies should determine the specific role of these four homeobox genes in the development and progression of human breast cancer and potentially determine if they might be good targets for gene therapy.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
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
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D005801 Genes, Homeobox Genes that encode highly conserved TRANSCRIPTION FACTORS that control positional identity of cells (BODY PATTERNING) and MORPHOGENESIS throughout development. Their sequences contain a 180 nucleotide sequence designated the homeobox, so called because mutations of these genes often results in homeotic transformations, in which one body structure replaces another. The proteins encoded by homeobox genes are called HOMEODOMAIN PROTEINS. Genes, Homeotic,Homeobox Sequence,Homeotic Genes,Genes, Homeo Box,Homeo Box,Homeo Box Sequence,Homeo Boxes,Homeobox,Homeoboxes,Hox Genes,Sequence, Homeo Box,Gene, Homeo Box,Gene, Homeobox,Gene, Homeotic,Gene, Hox,Genes, Hox,Homeo Box Gene,Homeo Box Genes,Homeo Box Sequences,Homeobox Gene,Homeobox Genes,Homeobox Sequences,Homeotic Gene,Hox Gene,Sequence, Homeobox,Sequences, Homeo Box,Sequences, Homeobox
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
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

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