[The possibility of the retroviruses participation in human breast neoplasm induction]. / O vozmozhnom uchastii retrovirusov v induktsii raka molochnoi zhelezy cheloveka.

The existence of retrovirus related to murine mammary tumor virus (MMTV) and specifically associated with mammary carcinoma has been suggested long ago. This review covers some papers published in the 70-80ies until now, containing evidence for this suggestion. In spite of a lack of direct proof of virus existence this problem still remains to be solved. There are some indications that both in man and in mice, peripheral blood lymphocytes participate in the circulation of the supposed viral agent.

[Effect of 5-azacytidine on expression of DNA sequences homologous to ENV gene of murine mammary tumor virus in normal human lymphocytes]. / Vliianie 5-azatsitidina na ékspressiu posledovatel'nostei DNK, gomologichnykh geny ENV virusa raka molochnoi zhelezy myshei, v limfotsitakh zdorovykh donorov.

Expression of DNA sequences, related to MMTV env gene, in peripheral blood lymphocytes, which was strictly specific for human mammary carcinoma, has been previously reported. These sequences (homologous to env gene site coding for MMTV gp52 envelope antigen) expressed in T cells can play the key role in virus infection transmission and propagation. In order to elucidate the possible routes of env MMTV-homologous sequences expression, we tried to induced it in donot T lymphocytes by various methods: hormone and virus treatment (related genome "saving" at the expense of the added virus envelope), T cell culturing with conA, interferon-2, and 5-azacytidine. RT-PCR with primers specific for the gp52-coding area of MMTV env gene showed expression of env-homologous sequences in donor T cells cultured in medium with 5-azacytidine. Indirect immunofluorescence with monospecific serum to MMTV gp52 detected gp52 analogous genes only in cultures with 5-azacytidine but not other agents. We therefore suggested that MMTV env-homologous sequences in donors are situated in the methylated promoter zone. Expression of these sequences in T cells, specific for human mammary carcinoma, can be due to demethylation of the promoter and induction of env-homologous sequences to the level of translation of gp52 analogous antigens or by initial location of some of the expressed sequences in the demethylated zone of the genome.

[An antigen related to the mouse mammary cancer virus env gene product, detected in human lymphocytes, is associated with human breast cancer]. / Antigen, rodstvennyi produktu gena env virusa raka molochnykh zhelez myshei, obnaruzhenny iv chelovecheskikh limfotsitakh, assotsirovan s rakom molochnyhkh zhelez cheloveka.

Expression of DNA sequences homologous to sequences of env gene of mouse mammary tumor virus (MMTV) in the lymphocytes of patients with breast cancer and in subjects at a high risk of breast cancer has been reported. Antigen analogous to envelope protein gp52, product of MMTV env gene, is detected in T lymphocytes of virtually all patients with breast cancer and extremely rarely in T cells of controls, where its expression is confined to B cells. For explaining such unexpected results, we studied the molecular basis of this antigen synthesis. Specific PCR products were obtained using primers to gp52-coding region of MMTV env gene. One of them (957 nucleotides) was used as a probe for hybridization of DNA and RNA from lymphocytes of patients with breast cancer and controls. This sequence was hybridized with 90% frequency with genome DNA of breast cancer patients and with 85% frequency with genome RNA of such patients, which is almost 4-fold more than in the controls (patients with gynecological tumors or donors). These results correlate with the frequency of detection of the studied antigen in patients with breast cancer and control group patients.

[Correlation between expression of antigen immunologically related to gp52 MMTV and transcription of homologous ENV MMTV DNA sequences in peripheral blood lymphocytes from breast cancer patients]. / Korreliatsiia mezhdu ékspressiei antigena, immunologicheski rodstvennogo gp52, i transkriptsiei gomologichnykh ENV MMTV posledovatel'nostei DNK v limfotsitakh perifericheskoi krovi bol'nykh rakom molochnoi zhelezy.

Previously we reported that HMCAg related to gp52, env product of MMTV, was a specific marker of human breast cancer (BC). This antigen was expressed not only in BC tissue and patients' sera, but in peripheral T- and B-cells. HMCAg was found in 21.4% of healthy donors, but only in the fraction rich in B-cells. We searched for env-homologous sequences in BC patients by Northern and Southern dot-blot hybridization of plasmid clones containing env MMTV with total RNA and DNA of peripheral blood lymphocytes of BC patients, gynecological patients with hormone-dependent tumors, and donors. Transcription of DNA sequences related to env MMTV was revealed in 91.3% of BC patients, 22.2% gynecological patients, and 27.2% donors. In all cases except 1 donor and 1 gynecological patient this transcription correlated with HMCAg expression in lymphoid cells from the same subjects detected by indirect immunofluorescence with anti-gp52 MMTV rabbit serum. Analysis of in vitro translation products with poly(A) RNA as a template and immunoblotting method showed that at least one of the polypeptides formed corresponded to HMCAg by molecular weight and immunological reactivity, which fact appears to explain the correlation described above.

[Correlation of MMTV antibody expression and risk factors of human breast cancer]. / Zavisimost' chastoty vyiavleniia antitel k MMTV u cheloveka ot faktorovriska raka molochnoi zhelezy.

Incidence of sera with antibodies to MMTV-related proteins has been studied in a cohort at high risk for breast cancer including healthy females and those with benign breast disease. The results were evaluated versus certain risk factors of breast cancer. No significant difference in the incidence was established between cases of diffuse fibrocystic mastopathy and healthy subjects. Nor was there any relationship between positive serum incidence and age, number of abortions, age at first childbirth or postmenopause. However, this parameter appeared to be in direct correlation with the number of childbirths (beginning from 3). This index was significantly higher in women (aged 40 and more) with early menarche than in those with medium and late menarche (8 and 0%, respectively).

[Humoral antibodies to structural proteins of murine mammary tumor virus as a potential immunologic marker of human breast cancer]. / Gumoral'nye antitela k strukturnym belkam virusa raka molochnykh zhelez myshei (MMTV) kak vozmozhnyi immunologicheskii marker raka molochnoi zhelezy cheloveka.

The presence of humoral antibodies specifically recognizing structural proteins of murine mammary tumor virus was studied in indirect immuno-enzymatic reaction, in 79 patients with suspected tumors of the breast. Diagnosis was verified after surgery by histological procedures. Said antibodies were detected in 13% of patients with benign tumors, lymphomas and mammary lymphosarcomas. However, in the breast cancer group including patients with T1-2N0M0 and T1N1M0, antibodies were identified in 85.7% of sera. It is suggested that patients with breast tumors who have antibodies to murine mammary tumor virus develop a specific nosological type of tumor which arises at reproductive age and is capable of high-rate growth and low-level metastatic spreading. Feasibility of application of said procedure for early detection of breast cancer is discussed.

[Presence of antibodies specifically reacting with structural proteins of the mammary cancer virus among antibodies found in circulating immune complexes in patients with breast cancer]. / Prisutstvie antitel, spetsificheski reagiruiushchikh so strukturnymi belkami virusa raka molochnoi zhelezy (MMTV), sredi antitel, vkhodiashchikh v sostav tsirkuliruiushchikh immunnykh kompleksov u bol'nykh rakom molochnoi zhelezy.

Circulating immune complexes were precipitated from breast cancer patients' sera using 2.5% polyethylene glycol. CIC isolated from 70 ml of sera from 15 patients were dissociated and immunoglobulin-containing fraction was prepared by chromatography on Sephadex G-200 column. The fraction contained IgG specific for MuMTV structural proteins, as revealed by ELISA. CIC preparations from 22 sera of breast cancer patients were digested with pepsin; Fab' fragment preparations were also analysed by ELISA, only one of them was MuMTV-specific. IgG and Fab' fragments isolated from CIC reacted specifically with MuMTV proteins, the reaction was not blocked by virus-free murine milk or other retroviruses (Ra-MuLV and MPMV).

[The antigen of transplantable cells immunologically related to the antigen of the normal human gastric mucosa]. / Izuchenie antigena perevivaemykh kletok, immunologicheski rodstvennogo antigenu normal'noi slizistoi obolochki zheludka cheloveka.

A newly detected antigen common for transplantable HeLa-like cell lines and human gastric mucosa has been revealed in all parts of the stomach and in highly differentiated gastric adenocarcinomas in humans. It is localized in the basal area of tall columnar cells in the mucosa and has one immunologically active subunit with molecular weight of 39 kDa. The antigen differs from the other earlier described gastrointestinal antigens in its localization in the organs and cells and in other characteristics.

[Specificity of antibodies against structural proteins of the mouse mammary cancer virus in healthy women and in mastopathy]. / Spetsifichnost' antitel k strukturnym belkam virusa raka molochnoi zhelezy myshei u zdorovykh zhenshchin i pri mastopatii.

The immunoenzyme technique was used to identify sera reacting with mouse mammary tumor virus (MMTV) proteins in patients with mastopathy and healthy subjects. Their specificity to certain viral proteins was established by immunoblotting. Serum samples obtained from 14 subjects reacted mainly with p27 MMTV, while those taken from another two subjects--mainly with gp52 virus. Humoral antibodies against p27 MMTV were found in 3.3% of the entire study group whereas anti-gp52 antibodies--in 0.5%.

[Endogenous MMTV in the normal mammary gland and in dimethylanthracene-induced mammary cancer in BALB/c mice]. / Endogennye MMTV v normal'noi molochnoi zheleze i indutsirovannom dimetilbenzantratsenom kantserogeneze molochnoi zhelezy myshei BALB/c.

Immunization of DMBA-treated mice by the glycoprotein fraction from mammary glands of mice BALB/c did not decrease the frequencies of induction of mammary tumors. This is in contrast to the results obtained during immunization by the formaldehyde treated preparation of Mouse Mammary Tumor Virus (MMTV). EcoRI and HindIII cleaved DNA from the DMBA-induced mammary tumors did not contain the additional virus specific fragments. In mammary tumors the expression of p27 MMTV was registered in contrast to normal mammary glands and mammary epithelium cultures in which the proteins of MMTV are not expressed even after induction.

[A protein related to the main core protein of the mouse mammary cancer virus in a microparticle fraction of human milk]. / Belok, rodstvennyi osnovnomu belku serdtseviny virusa raka molochnoi zhelezy myshei, vo fraktsii mikrochastits iz moloka cheloveka.

Virus-like density fractions (VDF) have been prepared from 6 specimens of human milk by ultracentrifugation of milk sera and recentrifugation of pellet through 35% sucrose or by separation in sucrose density gradient. Using electroblotting and enzyme-linked antibody probes, the protein with a molecular weight of 27 kD, reacting with serum against MMTV gag proteins, was identified in 5/6 of milk VDF. The absence (or very low amounts) of this protein among proteins of milk, fat globule membranes and cellular membranes of human milk has been demonstrated. Positive VDF decrease the activity of anti-p27 MMTV-specific serum and the activity of human sera reacting with p27 MMTV. A human protein immunologically related to the main gag protein of MMTV has been described; this protein seems to be an antigen causing the appearance of anti-MMTV antibodies in human sera.

[Antibodies interacting with the proteins of the mammary cancer virus (MMTV) in the sera of healthy women]. / Antitela, vzaimodeistvuiushchie s belkami virusa raka molochnoi zhelezy (MMTV) v syvorotkakh zdorovykh zhenshchin.

Using enzyme-linked immunoassay (ELISA), sera of 405 women without breast cancer were screened for the presence of antibodies to mouse mammary tumour virus proteins. 16 donors with positive sera were identified (3.96 +/- 0.97%). An attempt was made to establish the correlation between the age, ovarian Activity, benign breast disease and other factors and the appearance of antibodies to mouse mammary tumour virus. No statistically significant differences have been revealed among women aged 20-29 (3.92%), 30-39 (4.69%), 40-49 (4.08%) and 50-59 (2.38%), as well as in premenopausal (4.31%) and postmenopausal (4.5%) women and women with simple fibromatous disease (4.76%) and without any mammary gland pathology.

[Expression of antigens immunologically related to the antigens of the mouse mammary tumor virus in the tissue of human breast tumors]. / Ekspressiia antigenov, immunologicheski rodstvennykh antigenam virusa raka molochnykh zhelez myshei, v tkani opukholei molochnoi zhelezy cheloveka.

Indirect radioimmunoblotting on nitrocellulose filters and ELISA on polystyrene plates were employed to test the specimens of the normal and tumor tissue of the mammary gland for antigens which cross react with antigens of structural proteins of mouse mammary gland carcinoma virus. The antigens were detected in 9 tumor specimens out of 25 under testing and in 1 out of 15 specimens of the normal tissue. Such antigens failed to be detected in fibroadenoma or tumors of other sites.

[Molecular genetic bases of the oncogenic action of the mouse mammary tumor virus]. / Molekuliarno-geneticheskie osnovy onkogennogo deistviia virusa raka molochnykh zhelez myshei.

Processes associated with the neoplastic action of the mammary carcinoma virus on cells of the mammary gland myoepithelium are reviewed. Possible mechanisms of this action, stages of neoplastic process, at which the oncogenic MMTV potential is realized, and problems of virus and hormone cocarcinogenic action are discussed.

[Genome expression of endogenous type-B oncoviruses and carcinogenesis in the murine and human mammary gland]. / Ekspressiia genoma éndogennykh onkovirusov tipa B i kantserogenez v molochnoi zheleze myshei i cheloveka.

Data from literature and author's own experiments concerning conditions of the endogenous MuMTV genome expression and its influence on the organism are reviewed. Some findings on the expression in women of antigens related to the MuMTV antigens and antibodies to them are analyzed.

[Humoral antibodies to the antigens related to the structural protein antigens of the mammary cancer virus (MTV) in breast cancer patients and in healthy donors]. / Gumoral'nye antitela k antigenam, rodstvennym antigenam strukturnykh belkov virusa raka molochnoi zhelezy (MTV) u bol'nykh rakom molochnoi zhelezy i u zdorovykh donorov.

Indirect radioimmunoassay and immunoperoxidase studies provided further evidence of human serum reactivity with murine mammary tumor virus (MMTV) structural proteins. Examination of over 400 human sera from breast cancer (BC) patients and controls has shown that the incidence of antibodies which react with MMTV structural proteins was significantly higher in BC patients (50%) than in patients with carcinomas of other organs (3%) or normal women (3%). However, the percentage of subjects immune to MMTV was higher in pregnant women (10%) as compared with normal subjects. All the women with BC of the first clinical stage had antibodies to MMTV. The percentage of immune donors was lower among patients with BC of the later stages (IIa, 90%, IIb, 76%, III, 27%, IV, 0%). Thus, a good agreement has been demonstrated between the first stages of BC and expression of antibodies to MMTV.

[Expression of Thy 1 thymocyte differentiation antigen in mouse mammary cancer cells in vitro]. / Izuchenie ékspressii antigena differentsirovki timotsitov Thy 1 v kletkakh raka molochnykh zhelez myshei in vitro.

Allogeneic AKR-anti C3H Thy 1.2 antigen serum and monoclonal anti-Thy 1.2 and anti-Thy 1.1 antigen antibodies were used to study the expression of lymphocyte differentiation antigen in a clonal mammary carcinoma cell line originated from a GR/mt stable cell line. Both allogeneic antiserum and monoclonal anti-Thy 1.2 (but not Thy 1.1) antibody were active with the hormone-treated fixed cells in an indirect immunofluorescence test. However, antigen on the cellular membranes could be detected only with the use of allogeneic (but not with monoclonal antibody) anti-Thy 1.2 serum.

[Hormone-dependent enhancement of malignant phenotype in cells infected with mouse mammary tumor virus (MMTV), and role of antigen transduction in this process]. / Gormonozavisimoe povyshenie opukholevogo fenotipa kletok, zarazhennykh virusom raka molochnoi zhelezy myshei (MMTV), i rol' v étom protsesse transdutsiruemykh im antigenov.

Mouse mammary tumor virus (MMTV) is known to infect heterologous cells but it does not appear that it alters their growth or morphological characteristics. Djungarian hamster mammary tumor cells infected with MMTV were found to increase the ability of the above cells to grow in semi-solid media. This effect was demonstrable only in the presence of insulin and dexamethasone in cultural media. Meanwhile non-infected cells were discovered to show no responsiveness to hormones. The expression of non-viral antigen revealed by allogeneic anti-Thy 1.2 on the surface of infected cells was shown by the use of the cytotoxic test and immunofluorescence technique. However, the use of monoclonal anti-Thy 1.2 antibodies failed to prove that antigen in question was structural virion protein or Thy 1.2 antigen.