Mutation rate of MAP2K4/MKK4 in breast carcinoma.

Abstract:

: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.

journal_name

Hum Mutat

journal_title

Human mutation

authors

Su GH,Song JJ,Repasky EA,Schutte M,Kern SE

doi

10.1002/humu.9002

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

81

issue

1

eissn

1059-7794

issn

1098-1004

pii

10.1002/humu.9002

journal_volume

19

pub_type

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