Accession Number : ADB274458


Title :   Risk for Sporadic Breast Cancer in Ataxia Telangiectasia Heterozygotes


Descriptive Note : Annual rept. 1 Aug 2000-31 Jul 2001


Corporate Author : STATE UNIV OF NEW YORK AT STONY BROOK


Personal Author(s) : Moll, Ute M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b274458.pdf


Report Date : Aug 2001


Pagination or Media Count : 75


Abstract : The discovery of p73, a gene that in experimental conditions behaves like p53, requires us to determine what role it plays in breast cancer, whether a crosstalk exists between p73 and p53 actions and to delineate the differences and similarities between these two genes concerning their biological role and signaling pathways. Our understanding of p53's role in breast cancer has been made hazier again by the advent of p53's discovery. An additional challenge derives from the fact that the TP73 gene in principle can produce two diametrically opposed classes of protein products: full length forms and N-terminally truncated forms (that are missing the transactivation domain). Therefore, certain p73 isoforms could be dominant negative over p53 in heterotypic interactions. Conversely, it has already been shown that p73's transactivation and apoptotic function is inhibited by tumor-derived p53 mutants. This opens the possibility that the phenotype of mutant p53 tumor cells might in fact be due to an interference with normal p73 function. This scenario might explain why only 30% of breast cancers have mutated their p53 gene. In this case, dominant negative p73 isoforms, when deregulated in breast cancer, could interfere with p53 and p73-mediated growth suppression. We had previously reported that about 40% of breast cancers overexpress p73, indicating its role in breast cancer tumorigenesis. A better insight into p73's function will add greatly to our understanding of its role in this disease. (A) We showed that certain relevant oncogenes signal to p73 in vivo. Endogenous full length (TA) p73 alpha and beta proteins are upregulated and transcriptionally activated in p53-deficient tumor cells in response to deregulated oncogenes E2F1, c-MYC and E1A. Moreover, in the absence of p53, E2F1, c-MYC and E1A enlist p73 to induce apoptosis in tumor cells.


Descriptors :   *BREAST CANCER , RISK , PRODUCTION , BIOLOGY , PROTEINS , NEOPLASMS , SIGNALS , GENES , CELLS(BIOLOGY) , CROSSTALK , ATAXIA , ONCOGENIC VIRUSES


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE