Antibody Probes to Transcript-Specific Peptides Provide a Novel Tool to Investigate the Role of Alternate Estrogen Receptor Promoter Use in Breast Cancer
Annual rept. 1 Jul 2001-30 Jun 2002
HEALTH RESEARCH INC RENSSELAER NY
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Estrogen receptor alpha ER plays an important role in the development and progression of breast cancer, and it is routinely used as a marker for hormone sensitivity in breast cancer patients 1. Positive ER status is a useful indicator for a first-line therapy with antiestrogens 2. ER is expressed from at least two promoters Fig. 1. The resulting transcripts from these two promoters differ only in the non-coding region upstream of the major ER open reading frame ORF the ER proteins from these two promoters are identical. The proximal promoter transcript contains a 20 residue ORF which closes 52 nt upstream of the main ER ORF. which affects expression from the downstream ER ORF. Our central hypothesis is that the action of the proximal transcript uORF is exerted at the translation level. C-terminal truncated Phe20 or Gly 19 to stop prox-uORFs are highly effective and enhanced translational inhibitors. The presence of the natural C-terminal residue of the proximal uORF modifies weakens the inhibitory potential of the uORF. An ongoing goal aim is to under define critical regions for the inhibitory effect and to address mechanism.
- Medicine and Medical Research