Mutation rate of MAP2K4/MKK4 in breast carcinoma

Hum Mutat. 2002 Jan;19(1):81. doi: 10.1002/humu.9002.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Female
  • Humans
  • Loss of Heterozygosity / genetics
  • MAP Kinase Kinase 4*
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / genetics
  • Mice
  • Mice, SCID
  • Mitogen-Activated Protein Kinase Kinases / genetics*
  • Mutagenesis / genetics*
  • Mutation / genetics
  • Neoplasm Transplantation
  • RNA Splice Sites / genetics
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • RNA Splice Sites
  • MAP Kinase Kinase 4
  • MAP2K4 protein, human
  • Map2k4 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases