Antibody Probes to Transcript-Specific Peptides Provide a Novel Tool to Investigate the Role of Alternate Estrogen Receptor Promotor Use in Breast Cancer

摘要

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. Positive ER status is a useful indicator for a first-line therapy with antiestrogens. ER is expressed from at least two promoters (Fig.l) . 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 (Phe2O or Gly 19 to stop) prox-uORFs are highly effective and enhanced inhibitors of expression from the downstream ORF. We have data from the funded studies that supports the translational control hypothesis. The study has demonstrated conseouences of alternate promoter use beyond relative strength of the alternate promoters.