HOMEOBOX GENES - POTENTIAL CANDIDATES FOR THE TRANSCRIPTIONAL CONTROLOF THE TRANSFORMED AND INVASIVE PHENOTYPE

The transformation of a cell and the acquisition of the invasive and m etastatic phenotype result from the activation of a group of complex c ellular 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 gen es or orchestrator genes. The latter probably code for transcription f actors that control the genetic program for tumor invasion and metasta sis. Homeobox genes are a family of transcription factors that contain a 183 bp highly conserved nucleotide sequence coding for a 61 amino a cid domain that binds specifically to DNA. First discovered in Drosphi la as genes controlling segmentation and segment identity, homeobox ge nes have since been identified in many other species including nematod es, 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 th at are localized on chromosomes 2, 7, 12 and 17. The specific function s of each of these genes are generally unknown. Alterations in express ion of several homeobox genes have been reported in a variety of malig nant lesions, suggesting that they could play a role in the developmen t of cancer. Using reverse transcriptase reaction coupled with polymer ase chain reaction and degenerate oligonucleotides corresponding to th e 5' and 3' ends of the highly conserved homeodomain, we amplified 130 bp cDNA fragments from the human breast cancer cell line MCF7 that we re subsequently cloned into pBluescript vector. Sequencing of the clon es, resulted in the identification of the homeodomains of four differe nt human homeobox genes: HOXB6, HOXA1, HOXA10 and HOXC6. Further studi es 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.