Pseudotypes of vesicular stomatitis virus with envelope antigens provided by murine mammary tumor virus.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Dickson.
Explore the source record for details and available documents.
A short exposure of primary cultures of mouse mammary tumour cells to glucocorticoids results in at least a three-fold stimulation of mammary tumour virus (MTV) production. Specific interaction of glucocorticoids with the cytoplasmic and nuclear receptors can also be demonstrated. The biological potency of various steroids to stimulate MTV is related directly to the retention of the steroid-receptor complex in the nuclei. Progesterone has a high affinity for the cytoplasmic receptor, is not retained by the nuclei and does not stimulate or block the basal level of MTV production. It is, however, quite effective in abolishing the glucocorticoid-mediated stimulation of MTV and thus behaves as an antagonist of glucocorticoid.
Mouse mammary tumor virus polypeptides were detected in the cytoplasm of mouse mammary tumor cell cultures using immunological precipitation techniques. The anti-mouse mammary tumor virus serum precipitated the major virion glycoproteins gp49 and gp37.5/33.5 and a viral-related nonvirion glycoprotein of 76,000 daltons. Subcellular fractionation studies revelaed that the cell-associated virion glycoproteins were present in the membrane fraction. Pulsechase experiments indicated that a viral-related nonvirion glycoprotein of 76,000 daltons may be a precursor to one or more of the virion glycoproteins.
Mouse mammary tumor virus-producing cultures of mouse mammary tumor cells synthesize a viral-related polypeptide of molecular weight of 73,000 (gp 73) which is rapidly labeled during a short pulse but disappears during the chase concomitantly with the appearance of label in the virion glycoproteins gp 49 and gp 37.5/33.5. The addition of the protein synthesis-inhibitor cycloheximide to the chase medium has little effect on this conversion. Treatment of the proposed precursor with alpha-chymotrypsin leads to the formation of a polypeptide of molecular weight 49,000, similar to the major virion glycoprotein. A comparison of tryptic digest maps of the glycoproteins involved supports the hypothesis that both the viral glycoproteins gp 49 and gp 37.5/33.5 are derived from gp 73.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The role of steroids in promoting cell proliferation is well established but the molecular mechanisms are not clear. The S115 mouse mammary tumour cell line provides a model system for molecular studies in vitro in that it exhibits in tissue culture both a positive proliferative response to androgens and a change from a transformed phenotype in the presence of androgen to a normal phenotype when androgen is removed. We have considered here the possible involvement of mouse mammary tumour virus (MMTV) in these processes. We have demonstrated the presence in S115 cells of MMTV-related sequences which are transcribed into RNA only in the long-term presence of androgen. Prolonged culture in the absence of androgen, which results in loss of proliferative response to androgen, is accompanied by loss of MMTV-related RNA and increased methylation of MMTV-related sequences.
There is now good evidence that the induction of mammary carcinomas by mouse mammary tumour virus (MMTV) involves provirus activation of specific cellular genes. Thus, a high percentage of virally induced tumours contain an acquired MMTV provirus in either of two defined integration regions, termed int-1 and int-2, and provirus insertion is accompanied by expression of specific RNA transcripts from these regions. We show here that in some recurring, pregnancy-dependent mammary tumours provirus integration within int-2 has already occurred at the earliest appearance of the tumour and may therefore represent an important step in the development of neoplasia. As judged by the distribution of the acquired MMTV proviruses, the tumours recurring at any one site represent the same clonal population of cells as the original tumour and remain clonal during cycles of proliferation and regression, including the transition to hormone-independent status. These data suggest that either the expression of the int-2 locus or the function of this putative oncogene must remain responsive to hormones and that some additional event must be responsible for the transition to autonomous growth.
The induction of tumours by retroviruses lacking transduced oncogenes can involve the transcriptional or functional activation of cellular proto-oncogenes by an integrated provirus. Thus, the two cellular genes int-1 and int-2, identified as common targets for activation by mouse mammary tumour virus (MMTV), may constitute previously unrecognized oncogenes. In tumours, proviral insertion at these loci leads to expression of messenger RNAs which are undetectable in normal mammary glands. Here we report that in a survey of the two transcriptional activity and structural integrity of the two int loci in 30 BR6 mouse mammary tumours, around 50% of the tumours expressed both of these genes, in ostensibly monoclonal cell populations. Our data suggest that int-1 and int-2 may act cooperatively in the genesis of mammary carcinomas. However, because three tumours (10%) involved neither gene, and because in five cases activation occurred in the apparent absence of an adjacent provirus, it is clear that other loci and mechanisms contribute to tumorigenesis.
Explore the source record for details and available documents.
In the fourth paper in this urology series, bladder cancer and its treatment are discussed. The pre- and post-operative care and possible complications are described for the patient undergoing cystectomy and formation of ileal conduit. Psychological care following the stoma formation and the contribution of the stoma therapist are addressed.
Explore the source record for details and available documents.
Urology has developed historically into a specialty that continues to progress year by year. The needs of individuals within this specialty are varied and everchanging. In this, preliminary paper of the urology update series the diagnostic procedures concerned with urological disorders are examined. Subsequent papers will look at more specific urological conditions.
This paper examines diagnostic procedures for renal carcinoma and outlines surgical interventions, pre- and post-operative care and possible complications.