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.
Insogna
K L
KL
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Stewart
A F
AF
Morris
C A
CA
Hough
L M
LM
Milstone
L M
LM
Centrella
M
M
D002471:Cell Transformation, Neoplastic; D000242:Cyclic AMP / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D015291:Transforming Growth Factors / Q000494:pharmacology*
D005353:Fibronectins; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D000242:Cyclic AMP