Native and a synthetic analogue of the malignancy-associated parathyroid hormone-like protein have in vitro transforming growth factor-like properties.

A human parathyroid-like protein (PLP) has recently been isolated and cloned from human tumors associated with the paraneoplastic syndrome, humoral hypercalcemia of malignancy. PLP shares NH2-terminal amino acid sequence similarity with PTH but has a unique primary structure thereafter. Studies reported to date have indicated that both native and synthetic amino-terminal PLP polypeptides display actions in vivo and in vitro that are similar to those of PTH. We report here that purified native PLP and synthetic 36Tyr(1-36)amide human PLP induce epidermal growth factor-dependent transformation of NRK 49F cells in soft agar. Further, the synthetic peptide induces a significant increase in the biosynthesis of fibronectin by human dermal fibroblasts. (1-34)PTH does not display either of these biological activities. These data indicate that there are qualitative differences between PTH and the recently identified PLP. The latter hormone appears to possess transforming growth factor-like properties that may be relevant to its physiological actions.

[1]  A. Tomita.  [Hypercalcemia of malignancy]. , 1989, Rinsho byori. The Japanese journal of clinical pathology.

[2]  E. Brown,et al.  Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. , 1988, Molecular endocrinology.

[3]  E. C. Weir,et al.  Isolation of 16,000-dalton parathyroid hormone-like proteins from two animal tumors causing humoral hypercalcemia of malignancy. , 1988, Endocrinology.

[4]  G. Wesolowski,et al.  Comparison of postreceptor effects of 1-34 human hypercalcemia factor and 1-34 human parathyroid hormone in rat osteosarcoma cells. , 1988, The Journal of clinical investigation.

[5]  P. Barrett,et al.  Synthetic and partially-purified adenylate cyclase-stimulating proteins from tumors associated with humoral hypercalcemia of malignancy inhibit phosphate transport in a PTH-responsive renal cell line. , 1988, The Journal of clinical endocrinology and metabolism.

[6]  A. F. Stewart,et al.  Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. , 1988, The Journal of clinical investigation.

[7]  B. Kemp,et al.  Parathyroid hormone-related protein of malignancy: active synthetic fragments. , 1987, Science.

[8]  T. Clemens,et al.  Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro. , 1987, Science.

[9]  G. Strewler,et al.  Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. , 1987, The Journal of clinical investigation.

[10]  G. Vlasuk,et al.  Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone-like vasorelaxation in renal arteries. , 1987, Biochemical and biophysical research communications.

[11]  E. Chen,et al.  A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. , 1987, Science.

[12]  A. F. Stewart,et al.  N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. , 1987, Biochemical and biophysical research communications.

[13]  L. Suva,et al.  Parathyroid hormone-related protein purified from a human lung cancer cell line. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. F. Stewart,et al.  Skin-derived fibroblasts respond to human parathyroid hormone-like adenylate cyclase-stimulating proteins. , 1987, The Journal of clinical endocrinology and metabolism.

[15]  A. F. Stewart,et al.  Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. , 1987, The Journal of biological chemistry.

[16]  A. F. Stewart,et al.  Co-purification of transforming growth factor beta-like activity with PTH-like and bone-resorbing activities from a tumor associated with humoral hypercalcemia of malignancy. , 1987, Endocrinology.

[17]  H. Moses,et al.  Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. , 1987, The Journal of clinical investigation.

[18]  S. S. Huang,et al.  Transforming growth factor activity of bovine brain-derived growth factor. , 1986, Biochemical and biophysical research communications.

[19]  E. J. Zoelen,et al.  Transforming growth factor-beta and retinoic acid modulate phenotypic transformation of normal rat kidney cells induced by epidermal growth factor and platelet-derived growth factor. , 1986 .

[20]  J. Massagué,et al.  Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. , 1986, The Journal of biological chemistry.

[21]  A. F. Stewart,et al.  A parathyroid hormone-like protein from cultured human keratinocytes. , 1986, Science.

[22]  C. Osborne,et al.  Tumor-derived growth factor increases bone resorption in a tumor associated with humoral hypercalcemia of malignancy. , 1983, Science.

[23]  S. Bourgeois,et al.  Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts , 1983, Cell.

[24]  H. Moses,et al.  Comparison of intra- and extracellular transforming growth factors from nontransformed and chemically transformed mouse embryo cells. , 1983, Cancer research.

[25]  A. C. Webb,et al.  Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy. , 1988, Proceedings of the National Academy of Sciences of the United States of America.