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The effect of factors released from the tumor‐transformed cells on DNA synthesis, mitosis, and cellular enlargement in 3T3 fibroblasts
Author(s) -
Dafgård Eva,
Engström Wilhelm,
Larsson Olle,
Zetterberg Anders
Publication year - 1987
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.1041320214
Subject(s) - dna synthesis , 3t3 cells , mitosis , cell growth , cell cycle , cell division , cell , biology , reductase , microbiology and biotechnology , hmg coa reductase , cell culture , dna , enzyme , biochemistry , transfection , genetics
Quiescent serum‐starved 3T3 cells can be stimulated to initiate DNA synthesis after addition of conditioned media from spontaneously tumor‐transformed 3T3 cells (3T6‐cells) or from SV‐40‐transformed 3T3 cells (SV‐3T3 cells). The conditioned media were found to stimulate both the chromosome cycle (i.e, DNA synthesis and cell division) and the growth cycle (i.e., cellular enlargement). Furthermore, addition of conditioned media to quiescent 3T3 cells increased the activity of HMG CoA reductase—an enzyme previously proposed to exercise some control on cell proliferation in 3T3 cells Larsson and Zetterberg: J. Cell. Physiol. 129: 99–102, 1986. The increased activity of HMG CoA reductase after treatment with tumor cell conditioned media was correlated to the stimulatory effects on DNA synthesis. By treating 3T3 cells stimulated to resume proliferation by addition of conditioned media with mevinolin (a competitive inhibitor of HMG CoA reductase) the activity of HMG CoA reductase as well as the DNA synthesis and cell division were efficiently inhibited. In contrast, HMG CoA activity was not coupled to the cellular enlargement. Therefore, it is proposed that one set of factors present in tumor cell conditioned media preferentially stimulates the chromosome cycle by increasing the HMG‐CoA reductase activity, whereas another set of factors is responsible for growth in cell size. Both types of factors are required for balanced growth.