The cancer genes are comprised of a proliferation set (5 genes: Ki67, STK15, Survivin, CCNB1, MYBL2), estrogen hormone receptor genes (5 genes: ER, PGR, BCL2, SCUBE2), HER2neu set (2 genes: GRB7, HER2), invasion set (2 genes: MMP11
, CTSL2), and GSTM-1 (1 gene).
Different MMPs (MMP2, MMP9, MMP11
, and MMP14) and their expression were studied in the mesothelioma tissue, but only a few have been prognostically significant.
Xia et al., "Ectopic expression of miR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11
and VEGF," PLoS ONE, vol.
Collagenases (MMP-1, MMP-8, and MMP-13) and stromelysins (MMP-3, MMP-10, and MMP11
) are composed of a catalytic domain and a hemopexin-like domain.
Due to structural and substrate specificity, MMPs are currently divided into seven classes: collagenases (MMP1, MMP8, MMP13, and MMP18), gelatinases (MMP2 and MMP9), stromelysins (MMP3, MMP10), stromelysin like (MMP11
and MMP12), matrilysins (MMP7 and MMP26), membrane type (MMP14, MMP15, MMP16, MMP17, MMP24, and MMP25), and others (MMP19, MMP20, MMP21, MMP22, MMP23, MMP27, and MMP28) [18, 27, 28].
Os 16 genes incluem aqueles relacionados ao RE (ER, PR, BCL2 e SCUBE2), proliferacao (Ki67, STK15, Survivin, CCNB1 e MYBL2), HER2 (HER2 e GRB7), invasao (MMP11
e CTSL2), alem de tres genes adicionais relacionados (GSTM1, CD68 e BAG1).
Downregulated genes were those involved in proteolysis (MMP11
) and cell death, transcription factors, and the genes involved in the humoral immune response (CD24 antigen) .
Remarkably, increased expression of interstitial collagens, the main ECM components of the stroma, and many of their remodeling enzymes such as MMP1, MMP2, MMP11
, and MMP13, are frequently detected in gene signatures associated with poor prognosis in cancer patients (29).
While the majority of these 16 genes were found to be estrogen receptor-related (ESR1, PGR, BCL2, SCUBE2) and proliferation-related (Ki67, STK15, Survivin, CCNB1, MYBL2), some genes did not belong to these 2 categories (HER2, GRB7, MMP11
, CTSL2, GSTM1, CD68, BACG1).
Thus stromelysin 3 (MMP11
) is associated with the invasive phase of breast cancer, and much effort has been put into trying to design compounds that inhibit MMPs with a view to inhibiting tumour invasion.
(b) Gene symbol (c) Gene name (c) 2 PPM [O.sub.3] J02999 Rab2 ras-related protein RAB2 L19698 Rala GTP binding protein (Ral A) X07287 Pkrcg protein kinase C-[gamma] J03552 Mug1 plasma proteinase inhibitor D85760 Gna12 guanine nucleotide-binding protein a-12 M99567 PIcb3 phospholipase C [beta]-3 U00620 Cfs2 GM-CSF M59980 Kcnd2 voltage-gated K+ channel protein M83666 Hck Hck tyrosine protein kinase, p56 AF020777 Ptk2 focal adhesion kinase AF000300 Lyn lyn A tyrosine kinase 5 PPM [O.sub.3] U46034 Mmp11
matrix metal loproteinase 11 D55627 Rbl2 retinoblastoma-like 2 M95738 Slc6a11 Na+/K+ dependent GABA transporter M28647 Atp1a1 Na+/K+ATPaseed subunit U93306 Kdr VEGFR-2 M20637 Plcd1 phospholipase C delta 1 Accession no.
To date, there are 28 MMP family members described, including the collagenase subfamily (MMP-1, MMP-8, and MMP-13), the gelatinase subfamily (MMP-2 and MMP-9), the stromelysin subfamily (MMP-3, MMP-10, and MMP11
), membrane-associated MMPs (MMP-14, MMP-15, MMP16, MMP-17, MMP-23, MMP-24, and MMP-25), and other MMPs, all of which possess a Zn ion-dependent endopeptidase activity homologue domain [18-20].