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Calcium-induced matrix metalloproteinase 9 gene expression is differentially regulated by ERK1/2 and p38 MAPK in oral keratinocytes and oral squamous cell carcinoma.
J Biol Chem. 2004 Aug 06; 279(32):33139-46.JB

Abstract

Matrix metalloproteinases (MMPs) play an important role in the invasive behavior of a number of cancers including oral squamous cell cancer (OSCC), and increased expression of MMP-9 is correlated with invasive and metastatic OSCC. Because calcium is an important regulator of keratinocyte function, the effect of modulating extracellular calcium on MMP-9 expression in OSCC cell lines was evaluated. Increasing extracellular calcium induced a dose-dependent increase in MMP-9 expression in immortalized normal and premalignant oral keratinocytes, but not in two highly invasive OSCC cell lines. Differential activation of MAPK signaling was also induced by calcium. p38 MAPK activity was down-regulated, whereas ERK1/2 activity was enhanced. Pharmacologic inhibition of p38 MAPK activity or expression of a catalytically inactive mutant of the upstream kinase MAPK kinase 3 (MKK3) increased the calcium induced MMP-9 gene expression, demonstrating that p38 MAPK activity negatively regulated this process. Interestingly blocking p38 MAPK activity enhanced ERK1/2 phosphorylation, suggesting reciprocal regulation between the ERK1/2 and p38 MAPK pathways. Together these data support a model wherein calcium-induced MMP-9 expression is differentially regulated by the ERK1/2 and p38 MAPK pathways in oral keratinocytes, and the data suggest that a loss of this regulatory mechanism accompanies malignant transformation of the oral epithelium.

Authors+Show Affiliations

Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15180997

Citation

Mukhopadhyay, Subhendu, et al. "Calcium-induced Matrix Metalloproteinase 9 Gene Expression Is Differentially Regulated By ERK1/2 and P38 MAPK in Oral Keratinocytes and Oral Squamous Cell Carcinoma." The Journal of Biological Chemistry, vol. 279, no. 32, 2004, pp. 33139-46.
Mukhopadhyay S, Munshi HG, Kambhampati S, et al. Calcium-induced matrix metalloproteinase 9 gene expression is differentially regulated by ERK1/2 and p38 MAPK in oral keratinocytes and oral squamous cell carcinoma. J Biol Chem. 2004;279(32):33139-46.
Mukhopadhyay, S., Munshi, H. G., Kambhampati, S., Sassano, A., Platanias, L. C., & Stack, M. S. (2004). Calcium-induced matrix metalloproteinase 9 gene expression is differentially regulated by ERK1/2 and p38 MAPK in oral keratinocytes and oral squamous cell carcinoma. The Journal of Biological Chemistry, 279(32), 33139-46.
Mukhopadhyay S, et al. Calcium-induced Matrix Metalloproteinase 9 Gene Expression Is Differentially Regulated By ERK1/2 and P38 MAPK in Oral Keratinocytes and Oral Squamous Cell Carcinoma. J Biol Chem. 2004 Aug 6;279(32):33139-46. PubMed PMID: 15180997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium-induced matrix metalloproteinase 9 gene expression is differentially regulated by ERK1/2 and p38 MAPK in oral keratinocytes and oral squamous cell carcinoma. AU - Mukhopadhyay,Subhendu, AU - Munshi,Hidayatullah G, AU - Kambhampati,Suman, AU - Sassano,Antonella, AU - Platanias,Leonidas C, AU - Stack,M Sharon, Y1 - 2004/06/04/ PY - 2004/6/8/pubmed PY - 2004/10/27/medline PY - 2004/6/8/entrez SP - 33139 EP - 46 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 32 N2 - Matrix metalloproteinases (MMPs) play an important role in the invasive behavior of a number of cancers including oral squamous cell cancer (OSCC), and increased expression of MMP-9 is correlated with invasive and metastatic OSCC. Because calcium is an important regulator of keratinocyte function, the effect of modulating extracellular calcium on MMP-9 expression in OSCC cell lines was evaluated. Increasing extracellular calcium induced a dose-dependent increase in MMP-9 expression in immortalized normal and premalignant oral keratinocytes, but not in two highly invasive OSCC cell lines. Differential activation of MAPK signaling was also induced by calcium. p38 MAPK activity was down-regulated, whereas ERK1/2 activity was enhanced. Pharmacologic inhibition of p38 MAPK activity or expression of a catalytically inactive mutant of the upstream kinase MAPK kinase 3 (MKK3) increased the calcium induced MMP-9 gene expression, demonstrating that p38 MAPK activity negatively regulated this process. Interestingly blocking p38 MAPK activity enhanced ERK1/2 phosphorylation, suggesting reciprocal regulation between the ERK1/2 and p38 MAPK pathways. Together these data support a model wherein calcium-induced MMP-9 expression is differentially regulated by the ERK1/2 and p38 MAPK pathways in oral keratinocytes, and the data suggest that a loss of this regulatory mechanism accompanies malignant transformation of the oral epithelium. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15180997/Calcium_induced_matrix_metalloproteinase_9_gene_expression_is_differentially_regulated_by_ERK1/2_and_p38_MAPK_in_oral_keratinocytes_and_oral_squamous_cell_carcinoma_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15180997 DB - PRIME DP - Unbound Medicine ER -