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B R Henderson

Publications and source records attributed to B R Henderson.

29 records · Page 2Linked to original sources
PubMed1993

Dexamethasone decreases urokinase plasminogen activator mRNA stability in MAT 13762 rat mammary carcinoma cells.

The glucocorticoid dexamethasone was observed to decrease urokinase plasminogen activator (uPA) RNA levels from within 1 h of treatment of MAT 13762 mammary adenocarcinoma cells. The drug did not alter the rate of uPA gene transcription in these cells, but decreased the stability of cytoplasmic uPA mRNA transcripts. Results from cycloheximide and actinomycin D experiments indicated that the dexamethasone-mediated reduction in uPA RNA required both new protein and RNA synthesis. Based on these results, we propose that dexamethasone induces a short-lived protein(s) which down-regulates uPA RNA levels post-transcriptionally in these metastatic tumour cells.

Animals↗
PubMed1993

Expression of the nm23-2/NDP kinase alpha gene in rat mammary and oral carcinoma cells of varying metastatic potential.

Reduced expression of the putative metastasis-suppressor gene, nm23-1, has previously been correlated with high tumour metastatic potential. The involvement of the related and proximally-located nm23-2 gene in the suppression of tumour metastasis, however, has not yet been tested. In this study, we compared nm23-2 RNA levels in cell lines derived from three independent rat mammary carcinomas. Northern blot analysis revealed no correlation between nm23-2 RNA levels and metastatic potential in parent or clonal cell lines derived from chemically-induced (MAT 13762, DMBA-8) or spontaneous (BC1) rat mammary carcinomas. Cloning and sequencing of an nm23-2 cDNA from metastatic BC1 cells demonstrated that the predicted coding sequence of nm23-2 RNA in these cells was not inactivated by mutation. Further analysis showed that the nm23-2 gene was not down-regulated in H-ras-transfected metastatic clones or other metastatic cell lines derived from a spontaneous rat paraoral squamous cell carcinoma, B10. The data do not suggest a correlation between nm23-2 gene expression and metastasis-suppression in these tumours.

Animals↗
PubMed1992

TATA box-independent transcription of the human tissue plasminogen activator gene initiates within a sequence conserved in related genes.

Transcription of the human tissue-type plasminogen activator (tPA) gene has been reported to initiate from a single site proximal to a TATA box motif [1985, J. Biol. Chem. 260, 11223-11230]. In this study, we utilized primer extension analysis to evaluate the tPA mRNA start site in phorbol-12-myristate 13-acetate (PMA) induced WI-38 human lung fibroblast cells. Whilst some tPA mRNA initiated from the predicted TATA-proximal location (+1), a 10-fold greater proportion of tPA mRNA transcripts initiated 110 bases downstream from a sequence conserved and utilized as the TATA-independent transcription start site in the rodent tPA genes. Moreover, the transfection and expression in different cell types of a cosmid containing the entire human tPA gene resulted in utilization of the same downstream (+110) start site. We propose that this, rather than the previously published position, is the major transcriptional initiation point for the human tPA gene. A core sequence (5'-CAGAGCTG-3') was identified which is common to the TATA-independent mRNA start sites of the human, mouse and rat tPA genes, and which demonstrates only partial similarity to sequences found at the initiation point of other TATA-independent genes.

Amino Acid Sequence↗
PubMed1992

Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells.

Urokinase plasminogen activator (uPA) is a serine protease which has frequently been implicated in the process of tumor cell invasion and metastasis. The degree of expression and mode(s) of regulation of the uPA gene in metastatic compared with nonmetastatic tumor cells have not yet been addressed. We have cloned and sequenced a full-length rat uPA complementary DNA and utilized Northern blot analysis to report that the uPA gene is expressed at levels 3.5- to 70-fold higher in metastatic cell lines than in nonmetastatic cell lines derived from two independent rat mammary adenocarcinomas. Nuclear run-on assays and RNA half-life estimations indicated that metastatic MAT 13762 rat mammary adenocarcinoma cells expressed 3.5-fold higher levels of uPA RNA than a nonmetastatic derivative (J-clone), due to a combined increase in uPA gene transcription and cytoplasmic RNA stability. By contrast, uPA RNA (and enzyme) levels were elevated by up to 70-fold in metastatic clones of dimethylbenz(a)anthracene-induced rat mammary adenocarcinoma (DMBA-8) due to predominantly posttranscriptional mechanisms. Moreover, treatment of nonmetastatic DMBA-8 cell lines with protein synthesis inhibitors led to an increase in nuclear and cytoplasmic uPA RNA levels, without altering the rate of uPA gene transcription. These results suggest that in addition to gene transcription, posttranscriptional events localized in the nucleus and cytoplasm are key determinants of uPA gene activation in rat mammary adenocarcinomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Post-transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells.

The regulation of urokinase plasminogen activator (uPA) expression was investigated in 2 highly metastatic rat mammary adenocarcinoma cell lines, BC1 and MAT 13762. BC1 cells were observed to synthesize, on average, 10 times less uPA enzyme and mRNA than MAT 13762 cells; however this difference was not accounted for by differences in uPA gene copy number/structure or in the rate of uPA gene transcription in the cell lines studied. Moreover, Northern blot analysis of invasive sub-populations derived in vitro from the BC1 cell line revealed levels of uPA expression similar to those of the parent, but a 3-fold elevation in expression of the metalloprotease gene, transin. Further investigation showed that treatment of BC1 cells with either of the protein synthesis inhibitors, cycloheximide or anisomycin, increased the level of both nuclear and cytoplasmic uPA RNA 6- to 18-fold in 4 hr, whilst inducing a maximum 2.6-fold increase in the rate of uPA gene transcription. This increase in uPA gene expression may therefore reflect, in part, an increase in the stability and/or processing of nuclear uPA transcripts. These results suggest that the degree of uPA gene expression does not correlate directly with BC1 tumor-cell invasion in vitro, and that the uPA gene is down-regulated, at least in part, post-transcriptionally in the nucleus of BC1 mammary tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Subfamilies of serine tRNA genes in the bovine genome.

A bovine tRNA gene cluster has been characterized and the sequences of four tDNAs determined. Two of the tDNAs could encode tRNA(SerIGA), one tRNA(SerUGA), and the fourth tRNA(GlnCUG). The three serine tDNAs representing the UCN codon isoacceptor family are almost identical. However, the sequence of the tDNA(SerTGA) differs from a previously sequenced bovine tDNA(SerTGA) at 12 positions (ca. 14%). This finding suggests that in the bovine genome, two subfamilies of genes might encode tRNA(SerUGA). It also raises the possibility that new genes for a specific UCN isoacceptor might arise from the genes of a different isoacceptor, and could explain previously observed differences between species in the anticodons of coevolving pairs of tRNAs(SerUCN). The gene cluster also contains complete and partial copies, and fragments, of the BCS (bovine consensus sequence) SINE (short interspersed nuclear element) family, six examples of which were sequenced. Some of these elements occur in close proximity to two of the serine tDNAs.

Amino Acid Sequence↗
PubMed1987

The clinical management and laboratory assessment of anal warts.

The results of a clinical and virological survey of anal warts from 85 predominantly homosexual or bisexual men is presented, together with an improved technique for the surgical treatment of these lesions. Two types of anal warts, which were classified as either "acute" or "chronic" on the basis of their appearance and clinical behaviour, were recognized commonly. However, our laboratory investigations--which consisted of the routine histopathological examination of all specimens, together with immunohistochemical testing for the common wart antigen of specimens from 30 patients and papillomavirus typing by human papillomavirus DNA probing of 27 specimens--failed to reveal any significant differences between the two classes of anal warts. By means of a dot hybridization technique with mixed human papillomavirus DNA probes for types 6 and 11 and types 16 and 18, all wart biopsy specimens that were tested were shown to contain human papillomavirus types 6/11; two specimens also contained human papillomavirus types 16/18. Southern blot hybridization studies of eight specimens revealed that five warts contained human papillomavirus type 6 only and three warts contained human papillomavirus type 11 only. Although the surgical technique that is described was successful in terms of patient acceptance and the eventual eradication of anal warts, there was a high rate of recurrence of the lesions, which necessitated repeat operations in two-thirds of the patients. The need for counselling before surgery and for regular follow-up examinations after surgery is discussed.

Acute Disease↗
PubMed1987

Detection of specific types of human papillomavirus in cervical scrapes, anal scrapes, and anogenital biopsies by DNA hybridization.

Specific varieties of human papillomavirus (HPV) infecting the anogenital region were detected in clinical samples by use of a filter hybridization technique suitable for rapid screening of cervical and anal scrapes. In this way possibly benign types (HPV6 and HPV11) could be differentiated from types thought to be capable of malignant transformation (HPV 16 and HPV 18). Cervical or anal canal cells were applied directly to nylon filters and fixed by u.v. irradiation before hybridization with mixed viral DNA probes under both low- and high-stringency conditions. In addition, probe for the human Alu-repeated DNA sequence was used to assess the relative amount of total nucleic acids in each sample applied to the filter. HPV DNA was detected in 3 of 19 cervical scrapes from patients with no past or present history of wart virus infection or cervical dysplasia. Within a positive study group totalling 71 patients, HPV (6/11 or 16/18) was detected in cervical scrapes from 24% of 41 patients who did not have visible genital dysplasia, 30% of 27 patients with visible genital dysplasia or cervical intraepithelial neoplasia (CIN) I, and in 1 of 3 patients with past CIN II/III. In addition, HPV6/11 or 16/18 DNA was detected in anal scrapes from 3 of 6 male patients and in 85% of genital biopsies. A notably high proportion (4/6) of vaginal condylomata were positive with both the HPV6/11 and the HPV16/18 mixed viral DNA probes. Of the biopsies prepared for histopathology and positive for HPV DNA, the HPV group-specific antigen could be detected in only 60%.

Anal Canal↗
PubMed1987

Cell biology of cultured anogenital warts.

A simple, reliable culture system for keratinocytes from anogenital warts is described. Using this technique we found that it was possible to produce multiple confluent keratinocyte cultures from two-thirds of the surgically-excised anogenital wart specimens received in our laboratory. Some morphological and cultural differences between these cells and normal keratinocytes derived from neonatal foreskins were observed, although there was no evidence that wart-derived keratinocytes were 'transformed'. The cultures were tested for evidence of HPV-DNA replication using 32P-labelled HPV-DNA probes, for the production of viral capsid proteins using peroxidase-antiperoxidase staining and for whole virus particles using electron microscopy. Fifty-seven per cent (8 of 14) of the wart cultures tested showed persistence of HPV-DNA (5-100 copies HPV-DNA/cell genome equivalent). However, no viral proteins or particles were detected in any culture. This system may prove to be a useful in vitro model for the study of virus-cell interaction and the role of HPV in the malignant conversion of epithelial cells.

Anus Diseases↗
PubMed1975

Elevated serum levels of estrogen and prolactin in daughters of patients with breast cancer.

Demographic risk factors in sisters and daughters of 150 patients with breast cancer were compared to those of controls. Plasma hormone levels in 36 teen-age daughters of patients and 31 controls were also studied to ascertain whether an "abnormal" hormone pattern underlies these risk factors. The patients' sisters had, on the average, menarche four months earlier and first full-term pregnancy 12 months later than the controls. The patients' daughters did not show these differences -- apparently owing to low fertility in the patients with early menarche. The patients' daughters had higher 22d-day estradiol-plus-estrone levels than controls (24.4 vs. 19.1 ng per 100 ml, P less than 0.05). Sixth-day prolactin was also elevated (19.0 vs. 14.2 ng per 100 ml, P less than 0.05). About half the patients' daughters could clearly be distinguished from the controls' daughters by means of the sixth-day information on both estrogens and prolactin. Hypersecretion of these hormones may be important factors in breast cancer.

Adolescent↗