Accession Number : ADA349599


Title :   Transforming Growth Factor-B Receptors in Human Breast Cancer.


Descriptive Note : Annual rept. 1 May 97-30 Apr 98,


Corporate Author : YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE


Personal Author(s) : Reiss, Michael


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA349599


Report Date : MAY 1998


Pagination or Media Count : 47


Abstract : This project addresses the question whether and, if so, how molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We have cloned and determined the intron-exon structure of the TGFB type I receptor (TBR-I). This has allowed us to study this gene in a series of primary breast cancer specimens. Our most important finding is a much higher frequency of an exon 1 receptor variant among breast cancer cases than controls. Secondly, we have identified a serine to tyrosine mutation within the catalytic core of the TBR-I serine-threonine kinase domain in 2 of 31 primary and 5 of 12 metastatic breast cancer specimens. Thirdly, we have developed transient transfection as says to determine how specific TBR mutations affect receptor function. Using these assays we have shown that two previously identified TBR-II missense mutants are incapable of signaling because of the near complete loss of receptor kinase activity. Plans for the coming year include completing structural analyses of the TBR-I and -II genes in primary and metastatic breast cancer and defining the functional properties of the newly discovered TBR-I variant and mutant.


Descriptors :   *MOLECULES , *LESIONS , *BREAST CANCER , FREQUENCY , FUNCTIONS , TRANSIENTS , CORES , HUMANS , STRUCTURAL ANALYSIS , MUTATIONS , FUNCTIONAL ANALYSIS , CATALYSIS , GENES , CLONES , SENSE ORGANS , RECEPTOR SITES(PHYSIOLOGY) , TYROSINE , SERINE , METASTASIS , TRANSFECTION.


Subject Categories : MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE