The Role of Constitutively Active Prolactin Receptors in the Natural History of Breast Cancer
Abstract
Prolactin receptor (PRLR) is a single transmembrane receptor that normally requires ligand-binding to trigger intracellular signaling. Several isoforms of the human PRLR have been identified, including a long form (LF) and two short forms (SF1a and SF1b). These isoforms share identical amino acid sequence in the extracellular domain, but different cytoplasmic domain as a consequence of alternative splicing. The extracellular domain consists of two fibronectin-like subdomains, S1 and S2. Recently we have identified the existence of naturally-occurring S2 deleted (delta S2) variants in several human cancer cell lines. We also showed that these human delta S2 isoforms were constitutively dimerized in the absence of added PRL. When overexpressed in human breast cancer cells (T-47D) driven by a Tet-responsive promoter, the short isoform delta S2 SF1b produced prolonged activation of ERK and up-regulated both the cell cycle inhibitor, p21, and the milk protein, beta-casein. In this report, a soluble receptor lacking the S2 subdomain is also described. This isoform, termed SS1, is downregulated in human breast cancer and is capable of modulating PRL-stimulated signaling in T-47D cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA486217
Entities
People
- Kuang-tzu Huang
Organizations
- University of California Regents