Mutation rate of MAP2K4/MKK4 in breast carcinoma.
The stress-activated protein kinase (SAPK) pathways represent phosphorylation cascades that convey pro-apoptotic signals. The relevant inputs include Ras proteins as well as exposure of cells to ultraviolet light, tumor-necrosis factor, and other stress-related inputs. The mitogen-activated protein kinase kinase (MAPKK) homolog MAP2K4 (MKK4, SEK, JNKK1) is a centrally-placed mediator of the SAPK pathways. MAP2K4 mutations or homozygous deletions are reported in about 5% of a wide variety of tumor types. The exception is breast cancer, where genetic inactivation in 3 of 22 (15%) cell lines had suggested that the mutational involvement of MAP2K4 might be accentuated in this tumor type. This finding might have represented an important difference, or solely a chance numerical variation. To address this question, we studied an independent panel of 20 breast cancer cell lines and xenografts for MAP2K4 alterations. We found a splice acceptor mutation accompanied by loss of the other allele in the cell line MPE600. This was the sole alteration in this panel (5% of tumors). These data seem to re-establish a rather consistent rate of genetic inactivation of MAP2K4 among most tumor types, including breast cancer. The genetic evaluation of other mediators of the SAPK pathways might offer insight into a promising, but as yet poorly defined, tumor-suppressive system.
Su
Gloria H
GH
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Song
Jason J
JJ
Repasky
Elizabeth A
EA
Schutte
Mieke
M
Kern
Scott E
SE
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D048670:MAP Kinase Kinase 4; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics*; D016296:Mutagenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009368:Neoplasm Transplantation; D022821:RNA Splice Sites / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D022821:RNA Splice Sites; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases