Identification of Alternative Splicing Factors Involved in Prostate Cancer Progression

Abstract

The goal of this project is to identify and characterize proteins factors that regulate splicing of fibroblast growth factor 2 (FGFR2) in prostate cancer cells. A change in the splicing of this transcript has been shown to accompany the transition of model prostate cancers from an androgen dependent to androgen independent phenotype. It is hypothesized that the factors that control this splicing "switch" may be involved in the acquisition of androgen independent growth. To accomplish these goals, we are making use of a genetic screening strategy to identify splicing factors that specifically block the splicing of an exon, IIIc, whose inclusion is seen in androgen independent cancers. We have established reporter constructs in which splicing is required in order to restore an open reading frame (ORF)to a green fluorescent protein (GFP) expression plasmid. An adenoviral derived intron has placed in the GFP ORF and been shown to be efficiently spliced to yield GFP expression that can be identified by flow cytometry. We have inserted FGFR2 sequences containing ;This intron and been able to show cell-type specific splicing of exon IIIc. Currently we are further establishing the screen by optimizing exon IIIc splicing in GFP reporter contructs prior to performing cDNA screening.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2001
Accession Number
ADA407310

Entities

People

  • Russ P. Carstens

Organizations

  • University of Pennsylvania

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Androgens
  • Biomedical Research
  • Cell Line
  • Cells
  • Genes
  • Genetic Code
  • Genetic Structures
  • Genetics
  • Growth Factors
  • Identification
  • Inclusions
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Sequences
  • Transitions

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Prostate Cancer Biology.

Technology Areas

  • Biotechnology