Accession Number : ADA404992


Title :   Prevention of Breast Cancer Cell Transformation by Blockade of the AP-1 Transcription Factor


Descriptive Note : Final rept. 1 Sep 1996-30 Sep 2001


Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX


Personal Author(s) : Brown, Powel H


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a404992.pdf


Report Date : Oct 2001


Pagination or Media Count : 107


Abstract : We are investigating the role of AP-1 in controlling breast cell growth and transformation. We propose to determine the role of the AP-1 family of transcription factors in mediating peptide growth factor-induced proliferation and oncogene-induced transformation of breast cells. Previous results demonstrated that AP-1 complexes are activated by peptide and steroid growth factors in normal and malignant breast cells, and that normal breast cells express higher levels of AP-1 protein and activity than do breast cancer cells. We also previously showed that normal and immortal cells are more dependent on AP-1 for their growth than are most breast cancer cells. Over the last year, we determined whether AP-1 activation is required to transduce growth factor-induced signals in breast cancer cells. To perform these studies, we isolated MCF7 and MDA MB 435 clones that express a dominant-negative cJun mutant (TAM-67) under the control of an inducible promoter. These studies demonstrated that MCF7 cells, but not MDA MB 435 cells, depend on AP-1 for growth in serum. We also present results showing that inhibition of AP-i completely blocked MCF7 proliferation induced by IGF-1 and EGF, yet only partially inhibited growth induced by estrogen. These results demonstrated that the nitrogenic pathways in MCF7 cells activated by serum, estrogen, IGF-1, and EGF depend on AP-1 to transduce a proliferative signal, and that estrogen partially overcomes the growth suppressive effect of AP-1 blockade. These results suggest that AP-1 is a promising target of future cancer therapeutic and preventive agents since blocking this critical transcription factor suppresses proliferation induced by multiple growth factors.


Descriptors :   *CELLS(BIOLOGY) , *PREVENTIVE MEDICINE , *BREAST CANCER , PEPTIDES , PROTEINS , SUPPRESSION , TRANSFORMATIONS , GROWTH(PHYSIOLOGY) , STEROIDS , ESTROGENS , ONCOGENIC VIRUSES , TRANSCRIPTION(GENETICS) , ONCOGENESIS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE