The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression.
RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated protein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility. To assess whether RHAMM and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patients using reverse transcription-PCR and immunocytochemistry. We show that overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression. Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the primary tumor, and this staining pattern was associated with lymph node metastases. The metastases exhibited a significantly higher level of staining for RHAMM than did the primary tumor. RHAMM expression strongly correlated with overexpression of both ras and ERK, although overexpression of either of these two signaling molecules was not by itself a prognostic indicator. These results identify a new parameter that is involved in lymph node metastasis of primary breast cancers and suggest that quantification of RHAMM overexpression may be a useful prognostic indicator for breast carcinoma progression.
Wang
C
C
Department of Anatomy and Cell Biology, University of Toronto, and The Hospital for Sick Children, Ontario, Canada.
Thor
A D
AD
Moore
D H
DH
Zhao
Y
Y
Kerschmann
R
R
Stern
R
R
Watson
P H
PH
Turley
E A
EA
D001943:Breast Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000096:biosynthesis*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000096:biosynthesis*; D006820:Hyaluronic Acid / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D015398:Signal Transduction; D015996:Survival Rate; D013997:Time Factors; D018631:ras Proteins / Q000032:analysis
D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins