Cell shape and increased free cytosolic calcium [Ca2+]i induced by growth factors.

Growth factors stimulate DNA synthesis of neoplastic cells but not of non-neoplastic cells in suspension cultures. Similarly, growth ceases in dense monolayers of non-neoplastic cells, while crowded neoplastic cells continue to grow. The mechanism of these important phenotypic changes is unknown; the block in growth stimulation could occur in early events of signal transduction at the plasma membrane or in a late step in the final steps of gene activation and induction of DNA synthesis.

Effects of platelet-derived growth factor and fibroblast growth factor on free intracellular calcium and mitogenesis.

Although increased free intracellular calcium (Cai) may be one of the main regulators of cell growth and differentiation, studies in cell populations have implied that not all growth factors produce Cai increases. In order to examine in more detail whether Cai increases were related to mitogenesis, we used digital image analysis of intracellular Fura-2 fluorescence to measure Cai in individual BALB/c 3T3 cells stimulated with either platelet-derived growth factor (PDGF) or fibroblast growth factor (FGF). We found that PDGF induced larger and more prolonged Cai increases than FGF did, but that both growth factors induced an initial rapid increase in Cai (less than 2 min) followed by a later sustained increase (greater than 20 min).

Centrioles, primary cilia and calcium in the growth of Balb/c 3T3 cells.

In every mammalian cell the interphase centriole forms a primary cilium during some part of the cell cycle. Many sensory receptors are modifications of primary cilia, but a sensory role for primary cilia in mammalian cells has not been proven. Nevertheless, we have found that both growth factors and calcium ionophore (A23187) induce calcium fluxes and shortening of the primary cilium.

Stimulation of synthesis and secretion of chorionic gonadotropin subunits by eutopic and ectopic hormone-producing human cell lines.

The effects of dibutyryl cyclic adenosine 3'3':-5'-monophosphate (AMP) and sodium butyrate on the synthesis and secretion of human chorionic gonadotropin (HCG) by trophoblastic and nontrophoblastic human cell lines were studied by radioimmunoassay and pulse-chase labeling techniques. Dibutyryl cyclic AMP stimulated synthesis and secretion of HCG-alpha and HCG-beta subunits by the trophoblastic cell lines JAR and BeWo, whereas butyrate had no effect or decreased secretion. On the other hand, a number of nontrophoblastic cell lines (including the breast carcinoma lines ZR-75-31, BT-20, and MCF-7; the bronchogenic carcinoma line ChaGo; and the cervical carcinoma line HeLa S3) were induced to synthesize and secrete increased amounts of HCG subunits by butyrate, but dibutyryl cyclic AMP had less or no stimulatory effect.

Production of human chorionic gonadotropin and its subunits by human tumors growing in nude mice.

The production and secretion of human chorionic gonadotropin (HCG) and its subunits by human tumors growing in nude mice have been examined. JAR choriocarcinoma cells growing in nude mice produce both free alpha subunit and complete HCG, but there is a decrease in the amount of free alpha subunit relative to complete HCG produced in vivo compared to HCG subunit production by these cells growing in culture. Cell lines that produce only free alpha subunit in culture (HeLa cervical carcinoma, ChaGo bronchogenic carcinoma, and BT-20 breast carcinoma) continue to produce primarily free alpha subunit in vivo, but a small amount of HCG-beta/HCG is detectable in the 24-hr urine collected from mice bearing HeLa or ChaGo tumors.