TY - JOUR
T1 - Hyaluronidase activation of c-Jun N-terminal kinase is necessary for protection of L929 fibrosarcoma cells from staurosporine-mediated cell death
AU - Chang, Nan Shan
N1 - Funding Information:
Research was supported by the Guthrie Foundation for Education and Research, and the National Cancer Institute Grants CA61879 and CA64423. I thank Mr. John Heath and Ms. Lori Schultz for technical assistance, Dr. Roger Davis of the University of Massachusetts Medical Center for the JNK1 constructs, and Dr. Michael Kracht of the Medical School Hannover (Hannover, Germany) for the JNK2 and JNK3 constructs.
PY - 2001
Y1 - 2001
N2 - Hyaluronidase counteracts the growth inhibitory function of transforming growth factor beta (TGF-β), whereas secretion of autocrine TGF-β and hyaluronidase is necessary for progression and metastasis of various cancers. Whether hyaluronidase and TGF-β1 induce resistance to staurosporine in L929 fibrosarcoma cells was investigated. When pretreated with TGF-β1 for 1-2 h, L929 cells resisted staurosporine apoptosis. In contrast, without pretreatment, hyaluronidase protected L929 cells fromstaurosporine apoptosis. Hyaluronidase rapidly activated p42/44 MAPK (or ERK) in L929 cells and TGF-β1 retarded the activation. Nonetheless, TGF-β1 synergistically increased hyaluronidase-mediated inhibition of staurosporine apoptosis. Hyaluronidase rapidly activated c-Jun N-terminal kinase (JNK1 and JNK2) in L929 cells in 20 min. Dominant negative JNK1, JNK2, and JNK3 abolished the hyaluronidase inhibition of staurosporine apoptosis, but not the TGF-β1 protective effect. Unlike the resistance to staurosporine, pretreatment of L929 cells with hyaluronidase is necessary to generate resistance to other anticancer drugs, including doxorubicin, daunorubicin, actinomycin D, and camptothecin, and the induced resistance was also blocked by dominant-negative JNKs. Together, hyaluronidase-mediated JNK activation is necessary to generate resistance to various anticancer drugs in L929 cells.
AB - Hyaluronidase counteracts the growth inhibitory function of transforming growth factor beta (TGF-β), whereas secretion of autocrine TGF-β and hyaluronidase is necessary for progression and metastasis of various cancers. Whether hyaluronidase and TGF-β1 induce resistance to staurosporine in L929 fibrosarcoma cells was investigated. When pretreated with TGF-β1 for 1-2 h, L929 cells resisted staurosporine apoptosis. In contrast, without pretreatment, hyaluronidase protected L929 cells fromstaurosporine apoptosis. Hyaluronidase rapidly activated p42/44 MAPK (or ERK) in L929 cells and TGF-β1 retarded the activation. Nonetheless, TGF-β1 synergistically increased hyaluronidase-mediated inhibition of staurosporine apoptosis. Hyaluronidase rapidly activated c-Jun N-terminal kinase (JNK1 and JNK2) in L929 cells in 20 min. Dominant negative JNK1, JNK2, and JNK3 abolished the hyaluronidase inhibition of staurosporine apoptosis, but not the TGF-β1 protective effect. Unlike the resistance to staurosporine, pretreatment of L929 cells with hyaluronidase is necessary to generate resistance to other anticancer drugs, including doxorubicin, daunorubicin, actinomycin D, and camptothecin, and the induced resistance was also blocked by dominant-negative JNKs. Together, hyaluronidase-mediated JNK activation is necessary to generate resistance to various anticancer drugs in L929 cells.
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U2 - 10.1006/bbrc.2001.4701
DO - 10.1006/bbrc.2001.4701
M3 - Article
C2 - 11327694
AN - SCOPUS:0034805386
VL - 283
SP - 278
EP - 286
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -
