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Am J Physiol Cell Physiol 285: C1429-C1436, 2003. First published August 13, 2003; doi:10.1152/ajpcell.00269.2003
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GROWTH, DIFFERENTIATION, AND APOPTOSIS

Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells

Randolph H. Hastings,1,2,4 Flavio Araiza,1 Douglas W. Burton,1,3,5 Lu Zhang,1 Maxwell Bedley,1 and Leonard J. Deftos1,3,5

1Research, 2Anesthesiology, and 3Medicine Services, Veterans Affairs San Diego Healthcare System, San Diego 92161; and Departments of 4Anesthesiology and 5Medicine, University of California, San Diego, La Jolla, California 92093

Submitted 30 June 2003 ; accepted in final form 4 August 2003

Parathyroid hormone-related protein (PTHrP) is expressed in more advanced, aggressive tumors and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP-(1-34), PTHrP-(38-64), PTHrP-(67-86), PTHrP-(107-139), or PTHrP-(140-173) in media with serum, exposed for 30 min to UV-B radiation (0.9 mJ/cm2), and maintained for another 24 h. Caspase-3, caspase-8, and caspase-9 activities increased fivefold. Pretreatment with PTHrP-(1-34) and PTHrP-(140-173) ameliorated apoptosis after UV irradiation, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation, and increased clonal survival. Other peptides had no effect on measures of apoptosis. PTHrP-(140-173) also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase-3 or caspase-9 activity after 1 µM staurosporine. These data indicate that PTHrP-(1-34) and PTHrP-(140-173) protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.

caspases; cell surface receptors; growth substances


Address for reprint requests and other correspondence: R. H. Hastings, VA Medical Center (125), 3350 La Jolla Village Dr., San Diego, CA 92161-5085 (E-mail address: rhhastings{at}ucsd.edu).




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R. H. Hastings, F. Araiza, D. W. Burton, M. Bedley, and L. J. Deftos
Parathyroid hormone-related protein regulates apoptosis in lung cancer cells through protein kinase A
Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1616 - C1622.
[Abstract] [Full Text] [PDF]


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