A HUMAN LUNG-CANCER XENOGRAFT PRODUCING GRANULOCYTE-COLONY-STIMULATING FACTOR AND PARATHYROID HORMONE-RELATED PROTEIN

A human lung cancer xenograft, LC-GP, producing granulocyte-colony sti mulating factor and parathyroid hormone-related protein was establishe d by transplantation into severe combined immunodeficient (SCID) mice. The lung cancer patient and SCID mice bearing LC-GP showed leukocytos is and hypercalcemia. G-CSF and PTHrP gene expression were demonstrate d in the primary lung cancer, metastatic lesions and LC-GP xenograft. Immunohistochemical analysis confirmed the presence of G-CSF protein i n LC-GP xenograft cells. LC-GP possessed activated c-Ki-ras oncogene ( point mutation at codon 12). This LC-GP lacked apparent G-CSF receptor expression. The expression of G-CSF and PTHrP may be coregulated by t he activated c-Ki-ras oncogene, and autocrine stimulation of G-CSF is unlikely.