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F L Kisseljov

Publications and source records attributed to F L Kisseljov.

At least 19 recordsLinked to original sources
PubMed2006

Downregulation of genes encoding for subunits of adaptor complex-3 in cervical carcinomas.

We explored the expression of four genes encoding for subunits of AP-3 in cervical tumors and cancer cell lines. Using RT-PCR we demonstrated more than twofold decrease in the levels of mRNA of AP3D1, AP3B1, AP3M1, and AP3S1 in 32, 28, 23, and 26% tumors in comparison with normal tissues of uterine cervix, respectively. The level of mRNA of at least one subunit was decreased in 28 out of 47 (60%) of tumors and in four out of five cancer cell lines in comparison to tissues adjacent to tumors. The suppression of expression of any of the subunits was revealed in 15 out of 28 cases (54%). The expression of two and more subunits was decreased simultaneously in different combinations in 13 cases (46%). This fact testifies to the lack of a common mechanism of downregulation of four subunits in tumors. There is a tendency to more frequent suppression of AP-3A expression in tumors associated with lymphatic node metastases as compared with tumors without metastases (P = 0.034). Thus, here we demonstrate for the first time the decrease in expression of genes encoding for AP-3A subunits in tumors.

Adaptor Protein Complex 3↗
PubMed2005

DNA demethylation and carcinogenesis.

DNA methylation plays an important role in the establishment and maintenance of the program of gene expression. Tumor cells are characterized by a paradoxical alteration of DNA methylation pattern: global DNA demethylation and local hypermethylation of certain genes. Hypermethylation and inactivation of tumor suppressor genes are well documented in tumors. The role of global genome demethylation in carcinogenesis is less studied. New data provide evidence for independence of DNA hypo- and hypermethylation processes in tumor cells. These processes alter expression of genes that have different functions in malignant transformation. Recent studies have demonstrated that global decrease in the level of DNA methylation is related to hypomethylation of repeated sequences, increase in genetic instability, hypomethylation and activation of certain genes that favor tumor growth, and increase in their metastatic and invasive potential. The recent data on the role of DNA demethylation in carcinogenesis are discussed in this review. The understanding of relationships between hypo- and hypermethylation in tumor cells is extremely important due to reversibility of DNA methylation and attempts to utilize for anti-tumor therapy the drugs that modify DNA methylation pattern.

Animals↗
PubMed2001

Expression of cathepsin L and its endogenous inhibitors in immortal and transformed fibroblasts.

METHODS: The activities of cathepsin L and its endogenous inhibitors were analyzed in rat embryo fibroblasts, immortalized and transformed by different genes. RESULTS: Regardless of the transfecting agent used (DNA of adenovirus SA7 or polyomavirus LT gene), the immortal cells showed an increase in the cathepsin L activity (in both lysates and conditioned media) compared to primary fibroblasts. Transformed cells exhibited either an increase (with c-Ha-ras gene) or decrease (with E7 HPV gene) in cathepsin L activity in lysates as opposed to immortal cells. CONCLUSIONS: The data are suggestive of alterations in the trafficking of cathepsin L upon fibroblast transfection with polyomavirus LT gene and E7 HPV gene. An endogenous inhibitor(s) of cysteine proteinase was found in conditioned media, but not in lysates, of all cell cultures studied and its activity in normal fibroblasts was higher than in media of immortal and transformed cells.

Adenovirus E1A Proteins↗
PubMed2000

Virus-associated human tumors: cervical carcinomas and papilloma viruses.

The latest experimental data on the role of viruses in the origin of human tumors are discussed. This group of viruses consists of T-cell leukemia virus type 1 (HTLV 1), herpes viruses (HHV 8 and Epstein-Barr virus), hepatitis B virus, and human papilloma viruses. The most typical feature of this group of viruses is a very long latent period from the initial infection to the development of the disease that varies between 10 and 40 years. The mechanism of malignant cell conversion is specific for each viral type but is mainly associated with a disruption of functions of cellular genes participating in the control of cell division and proliferation. It can be a direct inactivation of tumor suppressor genes by their interaction with viral gene products (papilloma viruses), or a trans-activation of cellular genes modulating cell proliferation by viral gene products (hepatitis B virus and HTLV 1). Viruses play an initiative role and additional genetic changes in the genome of infected cells are necessary for complete expression of the oncogenic potential of the viral genes. Only these cells will give rise to a monoclonal cell population with uncontrolled proliferation. New approaches for the creation of vaccines against cancers associated with hepatitis B virus and papilloma viruses (hepatocellular carcinomas and cervical tumors, respectively) are in progress. These vaccines have been found to be effective in prevention of the disease in the experimental models and are now beginning to be used for human vaccination.

Cancer Vaccines↗
PubMed1998

De novo methylation of selective CpG dinucleotide clusters in transformed cells mediated by an activated N-ras.

We have explored a possible role of an activated N-ras oncogene in aberrant methylation of CpG clusters in DNAs of transformed cells. Using three lines of hamster cells transformed by Rous sarcoma virus (RSV) and the method of detection of CpG islands as clustered sites for methylation-sensitive restriction enzymes we have demonstrated that in each cell line the transcribed RSV proviruses are integrated in the vicinity of sequence containing the cluster of unmethylated CpG dinucleotides. Two out of three examined CpG clusters had hypermethylation patterns in N-ras-neo- but not in neo-transfected variants of the cell lines. De novo methylation of CpG dinucleotides correlated with transcriptional inactivation of adjacent RSV proviruses that was related neither to the lack of transcriptional factors binding RSV long terminal repeat (LTR) nor to the transcriptional incompetence of the LTR, as measured by reporter gene assays with the LTR cloned from DNA of these cells. These data suggest that activation of N-ras signal transduction pathway in transformed cells may be relevant to long-term inactivation of selective genes by hypermethylation of their CpG islands.

Animals↗
PubMed1995

HPV infection in cervical-cancer cases in Russia.

The presence of human papillomavirus (HPV) sequences in 21 biopsies from cervical carcinomas, 11 specimens of tissues adjacent to tumours, 2 specimens of cervical tissues with radiation fibrosis from patients after radiation therapy of cervical cancer and 7 normal epithelial tissues from the patients with other genital tumours were examined by polymerase chain reaction (PCR) and Southern-blot analysis. All tumours were HPV-positive by type-specific PCR and 86% by Southern-blot analysis. In normal epithelial and adjacent tissues, HPV sequences were detected in 20% of samples by Southern-blot analysis and in 70% of samples by PCR, including 2 cases of tissues after radiation therapy. HPV16 was the most prevalent type in tumours (18/21) as well as in normal epithelial tissues (5/7). One HPV-positive tumour contained HPV18 DNA and 2 were doubly infected with HPVs 16 and 18 (2/21). The persistence of exclusively episomal HPV16 DNA was observed in 5 out of 11 tumours examined: 3 cases of squamous-cell carcinomas on the early stage of tumour progression and 2 advanced tumours (squamous-cell carcinoma and adenocarcinoma). The integration of HPV16 genome was detected in 6 out of 11 tumours, but most of them contained episomal forms of viral DNA simultaneously (5 out of 6). The integrative HPV18 genome was found in 2 tumours examined, and the persistence of episomal forms was also observed in one of them. Our data demonstrate that cervical tumours are associated invariably with high-risk types of HPV in Russia.

Adenocarcinoma↗
PubMed1995

Proteolytic enzymes at various stages of oncogenic transformation of rat fibroblasts. I. Aspartyl and cysteine proteinases.

Aspartyl and cysteine proteinases at distinct stages of carcinogenesis were analyzed in rat embryo fibroblasts, sequentially immortalized and transformed by 2 different genes: the early region of simian adenovirus SA7 and c-Ha-ras oncogene. The dynamics of expression and distribution of proteinases throughout the transformation process were examined. It was shown that in immortalized and transformed cells the activities of the aspartyl and cysteine proteinases were expressed to a variable degree and that the expression was dependent on cell-propagation time in vitro. The increase in activity both of cathepsin-D-like aspartyl proteinase and of cathepsin-L- and -B-like cysteine proteinases in cell lysates was correlated with the stages of fibroblast transformation (immortalization and tumorigenic transformation). In all cell types the major part of cysteine proteinases was localized inside the cell, while the cathepsin-D-like proteinase was apparently predominant among secreted proteinases. The cathepsin-L-like proteinase accounts for the major part of the cysteine-proteinase activity as measured by Z-Phe-Arg-MCA hydrolysis. We suggest that considerable portions of the cathepsin-D- and -L-like proteinases in all cell lines studied are secreted as a complex with inhibitor(s) and that inhibitor expression plays an important role in regulating the activity of cathepsin-D-like proteinase at different stages of transformation. Cathepsin-L-like proteinase is probably secreted in the precursor form.

Amino Acid Sequence↗
PubMed1992

Changes in surface relief of suspended cells are morphological signs of the initial stage of neoplastic transformation in fibroblastic monolayer cultures.

The percentages of cells with different types of cell surface relief were determined in cell suspensions derived from monolayer cultures. Primary cultures of rat embryo fibroblasts (REF) and cell lines REF (LT) and REF-1, immortalized cells of which preserved normal phenotypic characteristics of the initial primary culture REF, as well as morphologically transformed tumorigenic lines REF (LT) ras and REF-2EJ were studied. In REF suspensions the cells with the blebbed type of surface relief were shown to be predominant as compared with those with microvillus relief whereas cell suspensions derived from both immortalized and fully transformed cultures display the reverse ratio of cells with those types of surface relief. Therefore, the pattern of cell surface relief in cell suspensions derived from fibroblastic monolayer cultures may serve as a morphological marker of the initial stage of neoplastic transformation-immortalization when typical morphological signs of cell transformation are not yet manifested in monolayer cultures.

Adenoviridae↗
PubMed1992

Expression of pp60c-src in human small cell and non-small cell lung carcinomas.

c-src protein was found in 60% of lung carcinomas (20 of 33 cases or primary tumours) by immunoblotting with a monoclonal antibody (Mab 327) and immunohistochemistry with serum from rabbits bearing tumours induced by Rous sarcoma virus. src protein expression was assessed in 4 small cell lung carcinomas and in an atypical carcinoid of neuroendocrine origin. However, pp60c-src was also found in non-small cell lung carcinomas: in 60-80% of adenocarcinomas and bronchiolo-alveolar cancers and in 50% of squamous cell carcinomas. In the squamous cell carcinomas, src protein was expressed more frequently in poorly differentiated than in well and moderately differentiated carcinomas. Expression of pp60c-src was not found in epithelial cells of histologically unchanged lung tissues. These results show that pp60c-src may be activated in human lung carcinomas of different histopathological types.

Adenocarcinoma↗
PubMed1992

Partial characterization of rat cell lines infected by a Rous sarcoma virus-33.

Rous sarcoma virus-33 (RSV-33) was obtained from a sample of chicken Rous sarcoma which had been dried and stored in 1933. RSV-33, like the RSV-29, has the minimal number of passages beyond its isolation from chicken tumour No. 1. Our experiments demonstrated that the Rous sarcoma virus-33 was replication non-defective and was pathogenic for rats. Established rat tumorigenic cell lines express the viral genome. All three species of viral RNA were detected and v-src proteins and gag polyproteins were identified as well in cells of R9 and R74 lines. The virus can be rescued from cells of R9 and R74 lines, thus indicating that the cells are virogenic. The cells of a permanent tumorigenic line RT1 are infected but not transformed by RSV-33. Although they contain a complete proviral genome, they do not express detectable virus-specific RNA. The virus is not rescuable from RT1 cells under in vivo conditions. Proviral DNA analysis showed that the RSV-33 contained a full-length genome, including the env gene, in contrast to the RSV-29 which was found replication defective.

Animals↗
PubMed1991

Transformation of rat-embryo immortalized fibroblasts by the E6-E7 region of human papillomavirus type 18.

Plasmids containing the E6 and E7 open reading frames of human papillomavirus type 18 transformed rat-embryo fibroblasts when expressed under the cytomegalovirus promoter. The fibroblasts had been previously immortalized with the large T-antigen gene of the polyomavirus to produce rat embryo fibroblast (large T-antigen) [REF(LT)] cells. REF(LT) cells were transformed by the E6 and E7 sequences to anchorage independence and tumourigenicity, but there were no significant morphological alterations. Transformation by these sequences of REF(LT) cells differed from that achieved by pEJras, in which case significant morphological changes and tumourigenicity in nude mice did occur.

Animals↗
PubMed1985

Oncogene expression in human tumors.

The expression of 9 oncogenes in primary tumors and in human tumors passaged in nude mice was tested: a total of 28 tumor types was analyzed. Oncogenes src, fps, and mos were not expressed in any of the tumors tested but oncogene myc was transcribed in most of the tumors and myc was over-expressed in 3 tumors passaged in nude mice (Ewing sarcoma, large intestine carcinoma and kidney carcinoma) and in primary fibrous histiocytoma. Enhanced transcription of ras and fos genes was observed nonspecifically in different tumors. Oncogene sis was activated specifically in metastases of different tumors in lymph nodes.

Animals↗
PubMed1984

Expression of RSV-specific proteins in RSV-transformed mammalian cells.

Expression of RSV-specific proteins was analysed in two virogenic and three helper-dependent RSV-transformed mammalian cell lines by the radioimmunoprecipitation technique. In all cell lines the only product of the gag gene was represented by the precursor Pr76gag without its further processing. The env gene was expressed in several lines in the form of 85K protein, but the product of this gene was absent in TWERC cells. The src gene product (pp60src) was identified by the protein kinase assay in all cells. In the kinase reaction in vitro, this protein can also phosphorylate some cellular proteins (130K, 34-36K and others) and the heavy chain of IgG.

Animals↗
PubMed1983

Differences in the organization and methylation patterns of integrated avian sarcoma proviral DNA sequences in nonpermissive and permissive mammalian cells.

Four types of avian sarcoma virus (ASV)-transformed mammalian cells were analyzed for the presence of ASV-specific sequences in their genome DNA. A great variability in the number of proviral copies and their structure within the DNA of these lines was observed. In all cells tested gag and src sequences were present in a flexible arrangement. The greatest variation was detected within proviral sequences corresponding to pol and env regions. The number of integrated ASV proviral copies do not correlate with the capability of these cells to produce viral particles. Virus-producing (K2S and K12) and virogenic (XC) cells contain in their chromosomal DNA at least one complete proviral genome, whereas proviral sequences in helper-dependent nonvirogenic cells are substantially changed. Provirus expression level does not correlate with the number of integrated virus copies. In the non-virus-producing cells the proviral sequences are hypermethylated.

Animals↗
PubMed1980

RSV-transformed mammalian cells: an analysis of RNAs specific for exogenous and endogenous viruses.

A marked decrease in expression of RSV-specific sequences was observed in cryptovirogenic RSV-transformed RVP3 murine cells during passaging. Simultaneously an increase in expression of sequences specific for C-type murine viruses was observed both in these cells and other RSV-transformed murine cells. No activation of C-type viral genome was detected in spontaneous murine lung tumors and in methylcholanthrene-induced murine tumors. Four types of virus specific RNAs were found in XC cells: the 30--35 S, the 26--28 S, the 21--23 S and the 15--18 S type. The 9--14 S RNA was the dominant species of RSV-specific RNA in TWERC cells.

Animals↗