Effects of serum, transforming growth factor type beta, or 12-O-tetradecanoyl-phorbol-13-acetate on ionized cytosolic calcium concentration in normal and transformed human bronchial epithelial cells.
Fluctuations in ionized cytosolic calcium ([Ca2+]i) are considered important signals for induction of growth or differentiation in mammalian cells. The resting concentrations of [Ca2+]i in normal and adenovirus 12-SV40 hybrid virus-transformed (BEAS-2B) human bronchial epithelial cells were 63 +/- 15 nM (SD) and 44 +/- 15 nM, respectively. Eight % calcium-free fetal bovine serum rapidly caused a significant increase in [Ca2+]i, while causing both cell types to undergo squamous differentiation. When treated with 8% calcium-free fetal bovine serum, a serum-sensitive subclone of BEAS-2B cells exhibited a higher elevation of [Ca2+]i than a serum-resistant (i.e., not stimulated to differentiate by serum) subclone. However, a serum component involved in the induction of squamous differentiation, transforming growth factor type beta, did not increase [Ca2+]i in either normal cells or BEAS-2B cells. 12-O-Tetradecanoyl-phorbol-13-acetate, an exogenous inducer of squamous differentiation and activator of protein kinase C, did not increase [Ca2+]i, but did attenuate serum-induced elevation of [Ca2+]i. These results suggest that while an increase in [Ca2+]i is associated with serum-induced squamous differentiation, a cytosolic ionized calcium signal is not required for the initiation of the squamous differentiation pathway induced by either transforming growth factor type beta or 12-O-tetradecanoylphorbol-13-acetate.
Miyashita
M
M
Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.
Smith
M W
MW
Willey
J C
JC
Lechner
J F
JF
Trump
B F
BF
Harris
C C
CC
D001790:Blood Physiological Phenomena; D001980:Bronchi / Q000032:analysis* / Q000187:drug effects; D002118:Calcium / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects; D003600:Cytosol / Q000032:analysis; D004848:Epithelium / Q000032:analysis; D006801:Humans; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015291:Transforming Growth Factors / Q000494:pharmacology*
D015291:Transforming Growth Factors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium