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Nuclear Expression of PTHrP and Outcome in Non-Small Cell Lung Cancer Randolph H. Hastings and Leonard J. Deftos VA PowerPoint Presentation
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Nuclear Expression of PTHrP and Outcome in Non-Small Cell Lung Cancer Randolph H. Hastings and Leonard J. Deftos VA

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Nuclear Expression of PTHrP and Outcome in Non-Small Cell Lung Cancer Randolph H. Hastings and Leonard J. Deftos VA San Diego Healthcare System Parathyroid Hormone-related Protein (PTHrP) Responsible for hypercalcemia of malignancy Homology with parathyroid hormone 1-34

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Nuclear Expression of PTHrP and Outcome in Non-Small Cell Lung Cancer Randolph H. Hastings and Leonard J. Deftos VA


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Nuclear Expression of PTHrP and Outcome in Non-Small Cell Lung CancerRandolph H. Hastings and Leonard J. DeftosVA San Diego Healthcare System

parathyroid hormone related protein pthrp
Parathyroid Hormone-related Protein (PTHrP)
  • Responsible for hypercalcemia of malignancy
  • Homology with parathyroid hormone 1-34
  • Reproduces the actions of PTH
  • Acts as a local growth factor
  • Expressed in all types of lung cancer
slide3

P

PTHrP Isoforms

slide4

P

PTHrP Processing

nuclear localization of pthrp
Nuclear Localization of PTHrP
  • Two nuclear localization sequences
  • NLS have clusters of basic residues
nuclear pthrp exerts intracrine effects
Nuclear PTHrP Exerts Intracrine Effects
  • Intracrine actions alter growth or apoptosis
  • Intracrine effects may oppose cell surface effects
opposing effects of pthrp on apoptosis in lung cancer cells
Opposing Effects of PTHrP on Apoptosis in Lung Cancer Cells
  • Paracrine effects protect.
  • Intracrine effects sensitize.
pthrp and cancer
PTHrP and Cancer
  • Expressed in many cancers, with and without associated hypercalcemia
  • Growth factor for many cancer cell lines
  • Favors bone metastasis in animal models
  • Associated with improved survival in breast cancer
hypothesis
Hypothesis

Nuclear expression of PTHrP and/or expression of PTHrP 1-173 increases survival in patients with non-small cell lung cancer.

evaluate survival as a function of pthrp expression
Evaluate survival as a function of PTHrP expression
  • Stain lung cancer sections for PTHrP protein and mRNA for the PTHrP isoforms.
  • Collect survival, stage, histology, age and gender data from computerized cancer registry
  • Analyze effect of PTHrP on 12-month survival with a Cox proportional hazards model
resources
Resources
  • Well established immunohistology laboratory
  • VA San Diego Cancer Registry (570 NSCLC patients)
  • UCSD Tumor Registry (1286 NSCLC patients)
  • UCSD Cancer Center Biostatistics Resource
opportunities for collaboration
Opportunities for Collaboration
  • Pathologist to assist with slide evaluation
  • Oncologist to discuss clinical relevance, consider future studies