An assessment of MMP and TIMP gene expression in cell lines and stroma - tumour differences in microdissected breast cancer biopsies.
To examine matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinases (TIMP) mRNA levels in archival breast cancer biopsies, we employed microdissection to separate tumour tissue from the surrounding breast tissue, or stroma and RT-PCR to determine gross qualitative and small quantitative differences in the patterns of expression. In this study, a significant correlation (p < 0.05, by Mann-Whitney U analysis) between TIMP-2 expression and lymph node involvement was identified, while MMP-11 and TIMP-1 expression patterning also significantly (p < 0.05) differed between those tumours showing calcification and those that did not. When compared by Spearmans' rho correlation analysis, a significant association (p < 0.05, rho = 0.404) was identified in the pattern of MMP-2 and MMP-9 gene expression. In this study, the use of microdissection and a systematic strategy of RT-PCR analysis have allowed us to investigate localized MMP and MMP inhibitor expression within breast tumours. We have identified patterns of gene expression that may further reveal aspects of breast carcinogenesis, and a robust method for examining changes in clinically important genes using archival biopsies and across stroma-tumour boundaries.
Genomics Research Centre, School of Health Science, Griffith University, Gold Coast Campus, Southport, Australia.
Albert S
AS
Mellick
Daneia
D
Blackmore
Stephen R
SR
Weinstein
Lyn R
LR
Griffiths
D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004210:Dissection; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics*; D017154:Stromal Cells / Q000473:pathology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases