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cAMP‐mediated growth inhibition of a B‐lymphoid precursor cell line Reh is associated with an early transient delay in G 2 /M, followed by an accumulation of cells in G 1
Author(s) -
Blomhoff Heidi Kiil,
Blomhoff Rune,
Stokke Trond,
Davies Catharina DeLange,
Brevik Kristin,
Smeland Erlend B.,
Funderud Steinar,
Godal Tore
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041370327
Subject(s) - forskolin , cell cycle , cell culture , cell growth , adenylate kinase , b cell , microbiology and biotechnology , cyclase , cell , adenosine , biology , activator (genetics) , chemistry , biochemistry , immunology , enzyme , antibody , genetics , gene
This study was undertaken to gain more insight into the effects of cyclic adenosine monophosphate (cAMP) on cell‐cycle progression in the B‐lymphoid precursor cell line Reh. The adenylate cyclase activator forskolin reduced the proliferation of asynchronously growing Reh cells by 50% after 72 hr culture. Growth inhibition was associated with an accumulation of cells in G 1 . Furthermore, we demonstrated that forskolin provoked a delay of cells for ∼ 10 hr in G 2 /M prior to the G 1 arrest. Two different methods were applied to elucidate how cells in different phases of the cell cycle were affected by an elevated cAMP level. One method was based on centrifugal elutriation, whereby synchronous cell populations from the different phases of the cell cycle were isolated. By the other method, S‐phase cells were selectively stained by pulsing asynchronously growing cells with bromo‐deoxyuridine (BrdU). The data demonstrate that the position of a cell in the cell cycle is critical in determining how the cell will respond to an elevated cAMP level. Thus cells in G 1 at the time forskolin is added are not delayed in G 2 /M, but they will subsequently accumulate in G 1 after 48 hr. Cells given forskolin in G 2 /M, however, are delayed for 10 hr in G 2 /M, but they do not accumulate in G 1 . Cells given forskolin in the S phase are delayed in G 2 /M as well as arrested in G 1 . The results suggest that cAMP inhibits growth of the Reh cells by preventing the cells from passing important restriction points located in the G 1 and G 2 phases of the cell cycle.