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Role of Parathyroid Hormone-Related Protein in Lung Cancer Cell Survival*

Randolph H. Hastings, MD, PhD; Flavio Araiza, BS; Douglas W. Burton, MS; Leonard J. Deftos, MD
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*From the Veterans Affairs San Diego Healthcare System, San Diego, CA 92161

Correspondence to: Randolph H. Hastings, MD, PhD, Associate Professor of Anesthesiology, Veterans Affairs San Diego Healthcare System, University of California, San Diego, 3350 La Jolla Village Dr, San Diego, CA 92161-5085; e-mail: rhhastings@ucsd.edu



Chest. 2004;125(5_suppl):150S. doi:10.1378/chest.125.5_suppl.150S
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Parathyroid hormone-related protein (PTHrP) has been studied extensively in lung cancer because of its relation to humoral hypercalcemia of malignancy. PTHrP is expressed in more advanced, aggressive tumors, and has effects on apoptosis in many malignant and nonmalignant cells. Thus, it also may play an active role in cancer progression.

We investigated the effects of PTHrP on apoptosis in BEN cells, a human squamous lung carcinoma line. Cells at 70% confluency were treated for 24 h with 100 nmol/L PTHrP 1–34, PTHrP 38–64, PTHrP 67–86, PTHrP 107–139, or PTHrP 140–173 in Roswell Park Memorial Institute medium/fetal bovine serum. Cells then were exposed for 30 min to 50 mJ/cm2 ultraviolet (UV)-B light. The activities of caspases 3, 8, and 9 increased fivefold 24 h after UV exposure. PTHrP 1–34 and PTHrP 140–173 reduced caspase 3 activity after UV exposure (mean [± SE] reduction, 19 ± 4% and 29 ± 7%, respectively), with similar effects on caspases 8 and 9. The two peptides increased cell protein levels, and PTHrP 140–173 augmented clonal survival after UV exposure. Other peptides had no effects. PTHrP 140–173 also reduced the activation of all three caspases after the ligation of Fas by neutralizing antibody, but neither peptide ameliorated the activation of caspases 3 and 9 after staurosporine administration, which elicited a solely mitochondria-dependent apoptotic pathway. UV light exposure causes Fas clustering, indicating that it initiates a death receptor pathway in BEN cells.

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