Expression and in vitro modification of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor in human myeloma cells.
To elucidate the role of PTHrP in myeloma, we examined the expression levels of PTHrP and its receptor in human myeloma cell lines and clinical specimens from 13 myeloma cases. In vitro modification of PTHrP expression and production induced by TGF-beta and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six out of seven myeloma cell lines with an inverse correlation with the expression of its receptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHrP expression and secretion into culture medium were enhanced by supplemental TGF-beta and PMA. PMA also seemed to affect PTHrP upregulation via TGF-beta activation. The fundamental role of PTHrP in bone lesions and hypercalcemia in myeloma may be important to consider even during the initial phase of the disease and particularly in the progression of bone complications with hypercalcemia.
Otsuki
T
T
Department of Hygiene; Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan. takemi@med.kawasaki-m.ac.jp
Yamada
O
O
Kurebayashi
J
J
Sakaguchi
H
H
Yata
K
K
Uno
M
M
Oka
T
T
Yawata
Y
Y
Ueki
A
A
D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016207:Cytokines; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D016212:Transforming Growth Factor beta; D012313:RNA; D013755:Tetradecanoylphorbol Acetate