Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in the process of tumor invasion and metastasis that are found throughout tissues and also in the plasma. The aim of this study was to investigate whether the evaluation of plasma concentrations of MMPs 2, 3 and 9 may have clinical significance in breast cancer. Therefore, sera obtained from 80 patients with breast neoplasia (50 carcinomas and 30 fibroadenomas) were collected before and 96 h after surgery and the concentrations of MMPs 2, 3 and 9 were quantified using an enzyme-linked immunosorbent assay (ELISA). The mean expression level of MMP 2 was significantly higher in carcinoma compared with that in fibroadenoma patients, while there was no significant difference for MMPs 3 and 9. In addition, the group of carcinoma patients was analyzed in order to compare the mean values for each MMP obtained before and after surgery. However, the differences between pre- and post-surgery values for all three MMPs were not statistically significant. Furthermore, the plasma levels of each MMP were correlated with certain clinicopathological parameters of the tumors and we observed a significant and direct correlation between the concentrations of MMPs 2 and 9 and tumor histological grade. These data suggest that the quantification of plasma MMP 2 and MMP 9 levels may provide additional clinical information of the tumor and it is, therefore, a possible prognostic index for breast cancer.

The MMS19 gene of the yeast Saccharomyces cerevisiae encodes a polypeptide of unknown function which is required for both nucleotide excision repair (NER) and RNA polymerase II (RNAP II) transcription. Here we report the molecular cloning of human and mouse orthologs of the yeast MMS19 gene. Both human and Drosophila MMS19 cDNAs correct thermosensitive growth and sensitivity to killing by UV radiation in a yeast mutant deleted for the MMS19 gene, indicating functional conservation between the yeast and mammalian gene products. Alignment of the translated sequences of MMS19 from multiple eukaryotes, including mouse and human, revealed the presence of several conserved regions, including a HEAT repeat domain near the C-terminus. The presence of HEAT repeats, coupled with functional complementation of yeast mutant phenotypes by the orthologous protein from higher eukaryotes, suggests a role of Mms19 protein in the assembly of a multiprotein complex(es) required for NER and RNAP II transcription. Both the mouse and human genes are ubiquitously expressed as multiple transcripts, some of which appear to derive from alternative splicing. The ratio of different transcripts varies in several different tissue types.

Cells from complementation groups A through G of the heritable sun-sensitive disorder xeroderma pigmentosum (XP) show defects in nucleotide excision repair of damaged DNA. Proteins representing groups A, B, C, D, F, and G are subunits of the core recognition and incision machinery of repair. XP group E (XP-E) is the mildest form of the disorder, and cells generally show about 50% of the normal repair level. We investigated two protein factors previously implicated in the XP-E defect, UV-damaged DNA binding protein (UV-DDB) and replication protein A (RPA). Three newly identified XP-E cell lines (XP23PV, XP25PV, and a line formerly classified as an XP variant) were defective in UV-DDB binding activity but had levels of RPA in the normal range. The XP-E cell extracts did not display a significant nucleotide excision repair defect in vitro, with either UV-irradiated DNA or a uniquely placed cisplatin lesion used as a substrate. Purified UV-DDB protein did not stimulate repair of naked DNA by DDB− XP-E cell extracts, but microinjection of the protein into DDB− XP-E cells could partially correct the repair defect. RPA stimulated repair in normal, XP-E, or complemented extracts from other XP groups, and so the effect of RPA was not specific for XP-E cell extracts. These data strengthen the connection between XP-E and UV-DDB. Coupled with previous results, the findings suggest that UV-DDB has a role in the repair of DNA in chromatin.