[Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, and metastatic colon tissue and colon biopsies from healthy donors]. / Sravnenie ékspressii mRNK matriksnykh metalloproteinaz v morfologicheski normal'noi, neoplasticheskoi i metastaticheskoi tkaniakh tolstogo kishechnika i v bioptatakh zdorovykh donorov.

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals.

[Mammaglobin in peripheral blood and tumor in breast cancer patients]. / Mammaglobin v perifericheskoi krovi i opukholi pri rake molochnoi zhelezy.

Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.

[DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues].

Extracellular glycoproteins of the laminin family are essential components of basement membranes involved in a number of biological processes, including tissue differentiation, wound healing, and tumorigenesis. We present the first comprehensive study of promoter methylation status of the genes encoding laminin chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells, autopsy breast tissue samples) and in breast carcinoma samples. Based on the results of this study, we divide laminin genes into three categories. Genes, constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1, LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group includes all of the genes that encode subunits of laminin-5 (the historical name of laminin 332), the promoters of which were previously considered unmethylated in normal tissues and prone to abnormal methylation in breast cancer.