Doctoral theses
Current Record: 968 of 1070
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| Identifier |
000029726 |
| Title |
Ρύθμιση του πρώτου ογκονιδίου H-ras1 από υποδοχείς Στεροειδών Ορμονών και την Ογκοκατασταλτική Πρωτεΐνη P53 |
| Alternative Title |
Regulation of the Hras1 Proto-onlogene from steroid Hormone Receptors and the P53 Tumour-supressor protein |
| Creator |
Zaxos, George
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| Abstract |
The ras family of cellular oncogenes is readily implicated in human tumorigenesis. Overexpression of ras oncogenes is associated with tumorigenicity, invasiveness and metastatic potential in a variety of human carcinomas, such as lung, gastric, head and neck, cervical, ovarian and breast cancer, indicating the importance of understanding the way ras genes are regulated. Steroid hormone receptors control gene expression as hormone-activated transcriptional activators, by specifically binding to palindromic DNA sequences, called hormone response elements (HREs). Steroids are considered to be tumor promoters and their levels influence the cure rates and survival of the patients with gynecological lesions. In our study, we showed that the human c-H-ras gene, contains within its first and fourth introns, sequences that are specifically recognized by glucocorticoid and estrogen receptors, respectively. We also examined the glucocorticoid and estrogen receptors tumorigenic potential in human endometrial and ovarian lesions, as compared to the adjacent normal tissue, and found elevated binding of steroid receptors in the H-ras elements in the majority of the tumor tissues tested. We therefore suggest that the H-ras proto-oncogene is hormonally regulated and that it is directly implicated in human gynecological cancer through elevated, steroid-induced gene expression. The p53 onco-suppressor gene is the most frequent target for genetic alterations in a wide variety of human cancers. The p53 gene product binds to DNA and activates transcription from promoters containing the consensus binding site. In our study, we showed that the human c-H-ras gene contains within the first intron sequences that are specifically recognized by the wild-type P53 protein and the "hot spot" mutant form His273, and determined that this element may act as a wild-type P53-dependent transcriptional activator. Furthermore, by examining the P53 status (wild-type or mutated protein) and its ability to specifically recognize the H-ras p53 element in nuclear extracts from human head and neck tumors and from adjacent normal tissue, we suggest that abnormal regulation of H-ras expression caused by alterations in p53 genetic locus, may play an essential role in human tumorigenesis.
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| Language |
Greek |
| Issue date |
1997-12-01 |
| Date available |
1998-04-5 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/2/c/1/metadata-dlib-1997zaxos.tkl
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| Views |
204 |
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