Evidence of MKK4 pro-oncogenic activity in breast and pancreatic tumors.
MKK4, located in close proximity to p53 gene, is thought to be a tumor suppressor and a metastasis suppressor gene. A low-rate MKK4 gene alteration has been found in a few tumor types, including breast and pancreatic. A suppressor activity for prostate and ovarian tumor metastasis has also been suggested. To understand the pathobiologic roles of MKK4 in tumorigenesis, we examined the phenotypic changes in response to perturbation of the MKK4 expression in breast and pancreatic cancer cell lines. Ectopic expression of MKK4 by adenoviral delivery in MKK4-negative cancer lines stimulated the cell proliferation and invasion, whereas knockdown of MKK4 expression by small interference RNA in an MKK4-positive breast cancer cell line, MDA-MB-231, resulted in decreased anchorage-independent growth, suppressed tumor growth in mouse xenograft model, and increased cell susceptibility to apoptosis brought by stress signals such as serum deprivation. These results argue that MKK4 functions as a pro-oncogenic molecule instead of a suppressor in breast and pancreatic tumors.
Wang
Lei
L
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pan
Yong
Y
Dai
Jia Le
JL
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology; D014183:Transplantation, Heterologous
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; C482562:Map2k4 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases