[Expression of p16INK4a in various cancer cells]. / Ekspressiia belka P16ink4a v kletkakh nekotorykh rasprostranennykh form raka.

The p16INK4a protein was detected by means of monoclonal antibodies to this protein in the cells of some carcinomas: that of the lungs (17 samples), urinary bladder (6 samples) and mammary gland (4 samples) as well as in the cells of three cell lines from of human uterine cervix carcinoma: SiHa (containing high risk HPV genome), C33A and HT3 (both HPV-negative but have RB mutations in RB gene). Lung carcinoma samples were very heterogenous by the part of cells expressing p16INK4a. High content of this protein was found in all 6 samples of transient cell urinary bladder carcinoma and in 1 sample of mammary gland ductal carcinoma. Cells of all three cell lines also contained p16INK4a. Thus, hyperexpression of this protein is not specific for only HPV-positive cancer of the uterine cervix. The protein presence in cancer cells seems to be an indicator of gene RB mutation or other disturbances of RB pathway.

[Expression of the protein marker p16INK4a in the cervix uteri cancer]. / Ekspressiia belkovogo markera p16INK4a v rake sheiki matki.

Immunohistochemical study was carried out of 18 cervical carcinomas (13 squamous and 5 adenomatous) and of 3 cases of cervical intraepithelial dysplasia. Formalin-fixed paraffin-embedded tissue samples from biopsies as well as from surgical material were used. Staining was performed with monoclonal antibodies to protein p16INK4a. Cytologic smears of epithelial cervical cells from 7 healthy women were taken as a negative control. The reference group consisted of 5 cancer patients with other tumors (breast cancer, B-cell lymphoma). Overexpression of p16INK4a was registered in cervical cancer.

[In vivo identification of YB-1 protein, interacting with the enhancer of human papillomavirus (HPV) type 18, using antibodies to a synthetic peptide]. / Identifikatsiia in vivo belka YB-1, vzaimodeistvuiushchego s énkhancerom virusa papilloma cheloveka (HPV) tipa 18 s pomoshch'iu antitel k sinteticheskomu peptidu.

Enhancer sequences of human papilloma virus (HPV) type 18 were used for screening of HeLa cells cDNA library in lambda gt11 using the protein binding method. Clones with YB I gene homology sequences were isolated. This gene is coding the protein which binds the regulatory region of Y gene of main histocompatibility complex (HLA 11). The YB I transcripts were revealed in all tested samples of cervical carcinomas. To analyze the protein the rabbit antibodies were produced to synthetic peptide, which corresponds to the most hydrophilic region of the protein. This antipeptide serum allowed to identify the nuclear 42K protein in HeLa cells as well as in normal fibroblasts.

[Structural changes of chromatin during proto-oncogene activation by cycloheximide: dose-effect]. / Strukturnye izmeneniia khromatina v protsesse aktivatsii protonkogenov tsklogeksimidom: doza-éffekt.

The level of expression of cellular proto-oncogens c-myc and c-fos in rat liver has been studied as a function of protein synthesis rate (cycloheximide dose). Activation of proto-oncogens has been established to be initiated by 50% inhibition of nuclear protein synthesis. This promotes a certain level in chromatin structural rearrangements which is manifested, in particular, in decreasing activity of chromatin cleavage by Ca2+, Mg(2+)-DNAase and increasing degree of chromatin condensation. A role of topoisomerase II in chromatin structural rearrangements during proto-oncogen activation is postulated.

[The effect of Ha-ras oncogene on cells immortalized by the gene for polyomavirus large T-antigen]. / Deistvie onkogena Ha-ras na kletki, immortalizovannye genom bol'shogo T-antigena virusa poliomy.

Activated human Ha-ras oncogene cloned on the plasmid pEJras6,6 was transfected into REF (LT) cells immortalized by the gene for large T-antigen of the polyoma virus. The cells were shown to become completely transformed (in the terms of morphology and tumorogeneity) only after three cycles of transfection with the plasmid pEJras6,6. The integrated sequences of the plasmid pEJras6,6 and the ras oncogene product p21Ha-ras were detected in cells only after their selection in the nude mice (in the cell culture REF (LT) ras X 3tu obtained from the tumor and directly in the tumor cells). Thus, after sequential transfections with a c-Ha-ras oncogene we developed cell cultures on the different stages of transformation process.

[C-src locus determines increased rate of Na+,K+-cotransport and increased calcium content in erythrocytes of (SHR x WKY) F2 hybrids]. / Lokus c-src opredeliaet uvelichennuiu skorost' Na+,K+-kotransporta i povyshennoe soderzhanie kal'tsiia v éritrotsitakh gibridov (SHR x WKY) F2.

26 male F2 hybrids between spontaneously hypertensive (SHR) and normotensive control (WKY) rats (SHRxWKY)F2 were segregated according to their c-src genotype into SS and WW homozygous groups, corresponding to SHR or WKY and WS heterozygous group. Na, K cotransport in erythrocytes in the WW group was equal to that of WKY and differs significantly from that of WS and SS groups (the rate of Na, K cotransport in latter groups was close to that of SHR). Ca content of RBC in WW group was equal to that of WKY, lower than that of WS and SS groups which in turn was significantly lower than in SHR, indicating polygenic control of the trait. Authors conclude that the c-src locus itself or some other loci inherited in conjunction with c-src determines both the increase of Na, K cotransport and calcium content in erythrocytes of SHR.

[Expression of oncogenes in the rat liver under conditions of template biosynthesis uncoupling by sublethal doses of cycloheximide]. / Ekspressiia onkogenov v pecheni krys v usloviiakh razobshcheniia matrichnykh biosintezov subletal'nymi dozami tsiklogeksimida.

Injection of sublethal doses of cycloheximide (CHI) to rats allowed to reveal three stages in the dynamics of protein synthesis: 1) suppression stage (0-6 hrs), 2) regeneration stage (6-12 hrs), 3) stimulation stage (6-12 hrs). RNA-polymerases are activated when protein synthesis is inhibited. The stimulation stage precedes the activation of DNA replication. This model of DNA replication induced by CHI is specified by the expression of various cell oncogenes (c-fos, c-mys, p53, c-Ha-ras, c-sis, c-src). The investigated oncogenes may be divided into 4 groups according to the character of their expression. 1. Oncogenes (c-fos, c-myc) are switched on step-by-step 1 hour after CHI injection, the superexpression of the oncogenes being comparatively short. Maximum expression of c-fos and c-myc oncogenes is registered after 2-3 hours, respectively. 2./p53 oncogene expression increases within a few hours' after CHI injection and manifests itself at all three stages of protein synthesis till DNA replication. 3. c-Ha-ras oncogene is expressed at a high level in control and experimental animals. 4. Expression of c-sis and c-src oncogenes are absent both before and after CHI injection. Sublethal doses of CHI have the same effect on oncogene expression as the lethal ones.

[Restriction fragment length polymorphism of c-fos and c-src oncogene loci in spontaneously hypertensive (SHR) and control (WKY) rats]. / Polimorfizm dliny restriktsionnykh fragmentov lokusov onkogenov c-fos i c-src u krys so spontannoi gipertenziei (SHR) i u kontrol'nykh krys (WKY).

Interstrain restriction fragments length polymorphism (RFLP) was detected after Southern blot hybridization of DNA from spontaneously hypertensive rats (SHR) and WKY rats treated with Bam HI restrictase with c-fos probe. The SHR genome is characterized by an additional miner band of 4.0 kilobase. RFLP was also revealed in c-src locus by Eco RI and Hind III restrictases. The major characteristic bands are 1.6 kb (SHR) and 2.4 kb (WKY) after Eco RI restriction and 3.4 kb (SHR) and 4.1 kb (WKY) after Hind III restriction. These RFLP can be used as mendelian traits in the linkage studies of distribution of blood pressure and other quantitative physiological traits in (SHR x WKY) F2 hybrids. The interstrain polymorphism determined in c-fos and c-src can also appear important in the evaluation of their physiological role in the cell.

[Cellular oncogene expression in human tumors transplantable to athymic mice]. / Ekspressiia kletochnykh onkogenov v opukholiakh cheloveka, perevivaemykh na bestimusnykh myshakh.

Expression of 3 cellular oncogenes among 7 ones under investigation is identified in the majority of 20 strains of human tumors, passaged in nude mice without significant specificity as far as the type of the tumor is concerned. The levels of the expression of these 3 oncogenes (c-myc, c-fos, c-ras) were higher than the ones in primary human tumors except for the human melanoma Mel-2 strain, where the expression of c-myb oncogene was identified. All the rest oncogenes (c-mos, B-lym, c-sis, c-myb) showed no expression in human tumors of the examined strains.

[Model systems of carcinogenesis in vitro: the interaction of the ras oncogene with immortalized cells]. / Model'nye sistemy kantserogeneza in vitro: vzaimodeistvie onkogena ras s immortalizovannymi kletkami.

Gene transfer experiments have shown that ras effector functions are sufficient to transform cells from a variety of established lines (e. g., mouse NIH3T3 cells). In contrast, primary cells and early passage rodent cells can be transformed by ras oncogenes only at low frequencies, unless cotransfected with collaborating genes such as adenovirus early region IA (EIA) or myc retroviral oncogene homologue. Primary rat embryo fibroblasts (REF) were chosen as a model for the analysis of multistep cellular transformation. Transfection of REF, immortalized by early region of simian adenovirus SA7 with c-Ha-ras oncogene cannot induce their morphological transformation. This phenomenon is observed only after second transfection with the same oncogene. These different cell lines can be used for further analysis of the mechanisms of carcinogenesis.

[Transcription of cellular oncogenes in human tumors]. / Transkriptsiia kletochnykh onkogenov v opukholiakh cheloveka.

The analysis of 11 various oncogenes expression in different human tumors showed that each tumor is characterised by a specific functioning program of these genes. In 40-50% of tumors the oncogenes ras, fos and myc are expressed. All other oncogenes are either considered to be "silent" or are expressed only in few cases. The increased expression of sis and myb oncogenes is observed in metastases.

[Cell oncogene expression in human stomach tumors]. / Ekspressiia kletochnykh onkogenov v opukholiakh zheludka cheloveka.

The paper is concerned with the analysis of expression of myc, myb, fos, ras and sis oncogenes in 11 gastric tumors of different histological patterns, 5 histologically-unaltered areas adjacent to tumor and in stomach tumor metastases into lymph nodes. A high frequency of myc, ras and fos oncogene expression was registered in all the types of tissue examined without any apparent signs of tissue specificity. The study failed to detect sis oncogene transcripts. The myb oncogene, generally dormant in solid tumors, was expressed in 2 gastric tumor metastases.