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Randolph H. Hastings, M.D., Ph.D.
Dr. Hastings’ laboratory studies mechanisms that regulate lung cancer progression, particularly involving parathyroid hormone-related protein (PTHrP). PTHrP is a paraneoplastic protein that is expressed in roughly two-thirds of all non-small lung carcinomas (NSCLC). The receptor for PTHrP is frequently present in lung cancers and is also made in pulmonary endothelial cells and other cells derived from normal lung. PTHrP exerts effects on cell growth, apoptosis and invasiveness. For example, Dr. Hastings has found that PTHrP modifies the sensitivity of lung cancer cells to apoptotic stimuli through a protein kinase A-dependent mechanism. Animal and patient studies in Dr. Hastings' laboratory indicate that PTHrP inhibits lung cancer growth and shortens patient survival. In patients with non-small cell lung carcinoma, tumor PTHrP expression is associated with longer survival consistent with an inhibitory effect of PTHrP on cancer. Interestingly, the protective effect of PTHrP occurs only in women, not in men. Ongoing work suggests that androgens inhibit lung cancer PTHrP expression through the Akt/MTOR pathway.
Selected Publications
Montgrain PR, Quintana R, Rascon Y, Burton DW, Deftos LJ, Casillas A, Hastings RH. Parathyroid hormone-related protein varies with sex and androgen status in nonsmall cell lung cancer. Cancer. 110:1313-20, 2007
Tsigelny I, Burton DW, Sharikov Y, Hastings RH, Deftos LJ. Coherent expression chromosome cluster analysis reveals differential regulatory functions of amino-terminal and distal parathyroid hormone-related protein domains in prostate carcinoma. J Biomed Biotechnol. 2005:353-63, 2005
Hastings RH, Laux AM, Casillas A, Xu R, Lukas Z, Ernstrom K, Deftos LJ. Sex-specific survival advantage with parathyroid hormone-related protein in non-small cell lung carcinoma patients. Clin Cancer Res. 12:499-506, 2006
Hastings RH, Araiza F, Burton DW, Bedley M, Deftos LJ. Parathyroid hormone-related protein regulates apoptosis in lung cancer cells through protein kinase A. Am J Physiol Cell Physiol. 287:C1616-22, 2004
Hastings RH, Araiza F, Burton DW, Zhang L, Bedley M, Deftos LJ. Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells. Am J Physiol Cell Physiol. 285:C1429-36, 2003
Hastings RH, Burton DW, Quintana RA, Biederman E, Gujral A, Deftos LJ. Parathyroid hormone-related protein regulates the growth of orthotopic human lung tumors in athymic mice. Cancer. 2001 92:1402-10, 2001
Deftos LJ, Burton D, Hastings RH, Terkeltaub R, Hook VY. Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues. Endocrine. 15:217-24, 2001
Hook VY, Burton D, Yasothornsrikul S, Hastings RH, Deftos LJ. Proteolysis of ProPTHrP(1-141) by "prohormone thiol protease" at multibasic residues generates PTHrP-related peptides: implications for PTHrP peptide production in lung cancer cells. Biochem Biophys Res Commun. 285:932-8, 2001
