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Monocytic differentiation and synthesis of proteins associated with apoptosis in human leukemia U‐937 cells acquiring resistance to Vincristine
Author(s) -
Pantazis Panayotis,
Chatterjee Devasis,
Han Zhiyong,
Wyche James,
DeJesus Albert,
Giovanella Beppino
Publication year - 1996
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1996.tb00494.x
Subject(s) - vincristine , apoptosis , biology , leukemia , microbiology and biotechnology , cell culture , cellular differentiation , monocyte , cell , cancer research , immunology , biochemistry , chemotherapy , gene , genetics , cyclophosphamide
Human leukemia U‐937/WT cells were exposed to stepwise increased concentrations of Vincristine so that Vincristine‐resistant cell sublines (termed U‐937/RV) were developed. Established U‐937/RV cell sublines have continuously propagated over a year, both in absence and presence of VCR, and have demonstrated similar features. In contrast to U‐937/WT cells, U‐937/RV cells have longer doubling time, and are more differentiated as determined by appearance of distinct morphological features and synthesis of mRNA that codes for the monocyte colonystimulating factor‐1 receptor ( c‐fms ). Both apoptosis‐suppressing Bcl‐2 and Bcl‐X L proteins were undectable in U‐937/WT cells, whereas Bcl‐2 was nearly detectable and Bcl‐X L readily detectable in U‐937/RV cells. The apoptosis‐promoting Bax protein was also absent in U‐937/WT cells and readily detected in U‐937/RV cells. Vincristine‐resistant cells with different levels of resistance synthesize similar levels of c‐fms mRNA and Bax protein. Finally, unlike U‐937/WT cells, U‐937/RV cells have no ability to induce tumors when xenografted in immunodeficient mice. The findings collectively suggest that development of resistance to Vincristine in U‐937/WT cells may correlate with cell differentiation and synthesis of proteins that regulate apoptosis.