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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The predominant effect of TGF-beta 1 on cell proliferation is inhibition. Earlier studies demonstrated that TGF-beta 1 inhibition of skin keratinocyte proliferation involves suppression of c-myc transcription and indirect evidence suggested that the protein product of the retinoblastoma gene (pRB) may be involved in this process. Skin keratinocytes transformed by SV40 and human papilloma virus-16 (HPV-16) or HPV-18 resisted growth inhibition and suppression of c-myc mRNA by TGF-beta. Transient expression of HPV-16 E7 gene, adenovirus E1A, and SV40 large T antigen (TAg) blocked the TGF-beta 1 suppression of c-myc transcription. Studies with transformation-defective mutants of E1A and TAg suggested that a cellular protein(s) that interacts with a conserved domain of the DNA tumor virus oncoproteins mediates TGF-beta 1 suppression of c-myc transcription and keratinocyte growth. Transient expression of pRB in skin keratinocytes repressed human c-myc promoter/CAT transcription as effectively as TGF-beta 1. The same c-myc promoter region, termed the TGF-beta Control Element (TCE), was required for regulation by both TGF-beta 1 and pRB. TCE bound a cellular protein of approximately 106 kDa and this binding was decreased by TGF-beta 1 treatment. Our data indicate that pRB can inhibit c-myc transcription and suggest the involvement of cellular factor(s) in addition to pRB in the TGF-beta 1 pathway for the suppression of c-myc transcription and growth inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1992 Jun
PMID:TGF-beta regulation of epithelial cell proliferation. 163 56

A reduction of gap-junctional intercellular communication (GJIC) often accompanies neoplastic transformation. The present work demonstrates that transformation by the oncogenic human DNA virus, human papilloma virus 16(HPV16), also reduces GJIC between L6 rat myoblasts. HPVs are associated with anogenital cancers, the incidence of which is increasing in HIV positive patients of both sexes. Using videofluorescence imaging of Fura-2 loaded cells a lack of GJIC between transformed HPV16-L6 cells was first indicated by uncoordinated brief [Ca2+]i spikes in clusters of DMSO-treated HPV16-L6 cells instead of the synchronous, sustained [Ca2+]i surges in clusters of DMSO-treated L6 cells. Reduced GJIC between HPV16-L6 cells was demonstrated directly by a much reduced transfer of lucifer yellow dye from HPV16-L6 cells, which had been loaded with the dye through electroporation with an EPIZAP II in situ electroporator, to neighbouring nonelectroporated HPV16-L6 cells. One reason for this reduced GJIC between HPV16-L6 cells could have been their dramatically enhanced activity of membrane-associated PKC which is known to phosphorylate connexins and down-regulate gap junctions. However, the main reason was the viral-induced inhibition of the expression of a major gap junction component, Cx43 (Connexin 43), in the transformed myoblasts.
Cell Mol Biol (Noisy-le-grand) 1995 Jun
PMID:Alterations in cell-cell communication in human papillomavirus type 16 (HPV16) transformed rat myoblasts. 754 85

To investigate the effect of tumor-associated macrophages on the in vivo growth properties of cervical carcinoma cells, tumorigenic human papilloma virus (HPV) 18-positive HeLa cells were transfected with an expression vector harboring the cDNA for the macrophage chemoattractant protein-1 JE (MCP-1). Although the endogenous gene is present and not structurally rearranged, its expression seems to be negatively affected by a still unknown mechanism. Inoculation of JE (MCP-1)-negative HeLa cells into nude mice led to rapidly growing tumors, where macrophage infiltration into the inner tumor mass was not detectable immunohistochemically. The activity that attracted mononuclear cells under both in vitro and in vivo condition was reconstituted in HeLa cells after transfection with the JE (MCP-1) expression vector. Heterotransplantation of those cells into immunocompromised animals resulted in significant growth retardation that was accompanied by a strong infiltration of macrophages. On the other hand, in vivo selection of nonmalignant hybrids made between wild-type HeLa cells and normal human fibroblasts in nude mice resulted in tumorigenic segregants 4 mo after inoculation into the animals. Monitoring JE (MCP-1) expression directly within those nodules, we found that transcription was either absent or only weakly detectable. Recultivation of JE (MCP-1)-positive tissue grafts under in vitro conditions revealed that the gene was only marginally inducible by tumor necrosis factor-alpha, a cytokine that normally induces a very strong activation of transcription in nontumorigenic cells. These findings suggest that functional JE (MCP-1) expression and in turn activated macrophages may play a pivotal role in controlling the proliferation rate of HPV-positive cells in vivo.
Mol Carcinog 1995 Nov
PMID:The effect of the JE (MCP-1) gene, which encodes monocyte chemoattractant protein-1, on the growth of HeLa cells and derived somatic-cell hybrids in nude mice. 757 10

Glucocorticoid hormones positively regulate human papilloma virus (HPV) type 16 gene expression, and we have previously shown that this regulation is through three glucocorticoid response elements (GREs). The GRE at nucleotide 7640 is a composite GRE (cGRE) containing an overlapping activator protein-1 (AP-1) motif for the c-jun homodimer and c-jun/c-fos heterodimer. This report examined the effects of c-jun and/or c-fos AP-1 protooncogenes and the glucocorticoid hormone dexamethasone on expression of the HPV 16 cGRE in AP-1-deficient P19 embryonal carcinoma cells. The activity of the full-length HPV 16 enhancer was progressively increased with increasing levels of c-jun. The hormone induced an additional response. For the c-jun/c-fos heterodimer, the response to hormone was progressively diminished. Site-specific mutations of the cGRE revealed that the regulation by AP-1 and hormone required both GRE and the AP-1 motif. An enhancer fragment containing the cGRE and excluding the two simple GREs gave similar results. Two disruption mutations of the AP-1 site confirmed the requirement of this site for hormone response. A cGRE oligonucleotide construct substantiated the effect of c-jun for response to hormone. For heterodimer, activity and hormone response were both also progressively increased. The results reveal a unique cross-talk between the distinct AP-1- and hormone-signaling pathways, suggesting the involvement of a complex interaction of c-jun and c-fos and glucocorticoid hormone receptor with the HPV 16 cGRE, resulting in novel control patterns for regulating viral expression.
Mol Endocrinol 1994 Dec
PMID:Differential regulation by c-jun and c-fos protooncogenes of hormone response from composite glucocorticoid response element in human papilloma virus type 16 regulatory region. 770 58

To conduct studies on the clinical and pathologic significance of human papilloma virus (HPV) in genital malignancies, accurate detection and typing of the virus in clinical material are essential. Currently, Southern blotting and the polymerase chain reaction (PCR) are two of the most commonly used methods to identify HPV. This study was undertaken to compare these techniques in the detection and typing of HPV in 242 invasive malignancies of the lower female genital tract. BamHI and PstI restriction digests of tumor DNA were hybridized to 32P-labeled probes for HPV types 6, 16, and 18 at TM -20 degrees C after Southern transfer. Blots were then washed at Tm -20 degrees C and Tm -9 degrees C. The DNA was also amplified by PCR using both highly conserved consensus L1 primers that detect 25 different HPV genotypes and primers specific for HPV 6 E6, 16 E7, and 18 E6. All PCR products were hybridized to type-specific radiolabeled probes. In 202 of the 242 (83%) samples, HPV was detected, including 189 of 218 (87%) cervical cancers, 11 of the 20 (55%) vulvar cancers, and two of four tumors from the vagina, urethra, or anus. In 67% of the specimens, there was agreement between the Southern blot technique and both methods of PCR (consensus and type-specific primers), including 121 of the 202 HPV-positive specimens and 40 HPV-negative specimens. Of the 141 tumors with HPV detected by Southern blot analysis, the same HPV type was detected by PCR in 121 (86%).(ABSTRACT TRUNCATED AT 250 WORDS)
Diagn Mol Pathol 1994 Dec
PMID:Comparison of the polymerase chain reaction and Southern blot analysis in detecting and typing human papilloma virus deoxyribonucleic acid in tumors of the lower female genital tract. 786 40

In order to identify genes in the Prader-Willi/Angelman syndrome critical region, radiolabeled cDNA probes from poly(A)+ RNA from mouse tissues were used to identify potential exon-containing genomic DNA fragments in cosmid or phage clones from appropriate yeast artificial chromosomes, and these fragments were subsequently used to screen human cDNA libraries. A mouse brain cDNA probe was effective in detecting control genes of various abundance including small nuclear ribonucleoprotein polypeptide N (SNRPN), hypoxanthine-guanine phosphoribosyl transferase, glyceraldehyde-3-phosphate dehydrogenase, and beta-actin. Two genes mapping within the Angelman syndrome critical region were isolated. One gene was found to encode the E6-associated protein (E6-AP; gene symbol HPVE6A), a protein which interacts with the E6 protein of human papilloma virus. The other gene is previously uncharacterized and is designated PAR-2 (D15S225E) for Prader-Willi and Angelman region-gene 2. Imprinting analysis using reverse transcription-polymerase chain reaction of RNA from fibroblasts and lymphoblasts of deletion Prader-Willi and Angelman patients demonstrated imprinting of SNRPN with exclusive expression from the paternal allele, but E6-AP and PAR-2 were not imprinted in these cultured human cells. The ability to analyze for imprinting and expression of SNRPN and other genes in this region in cultured human cells will be a valuable tool for analyzing the molecular basis of the Prader-Willi and Angelman syndromes, although imprinting may differ between cultured cells and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Hum Mol Genet 1994 Feb
PMID:Imprinting analysis of three genes in the Prader-Willi/Angelman region: SNRPN, E6-associated protein, and PAR-2 (D15S225E). 800

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.
Mol Biol (Mosk)
PMID:[In vivo identification of YB-1 protein, interacting with the enhancer of human papillomavirus (HPV) type 18, using antibodies to a synthetic peptide]. 838 54

A polymerase chain reaction (PCR) based technique that combines a virus specific primer and a human interspersed repetitive sequence (IRS) specific primer in order to detect integration of human papilloma virus type 16 (HPV-16) is described. Amplification of viral-host DNA junctions occurs when viral integration results in placement of the virus specific primer binding site near (less that 3-4 kb) the primer binding site within a repetitive sequence element. The method relies on enzyme labeled oligonucleotide probes to achieve rapid, specific, and nonradioisotopic detection of viral integration related PCR products since episomal forms of the viral DNA do not lead to exponential accumulation of hybridizable PCR products. The technique is demonstrated for human genomic DNA derived from clinical cervical swab specimens and archival paraffin embedded blocks. Viral integration was detected in 41% of the HPV-16 positive samples (n = 34). In this positive subset, 64% were classified as invasive neoplasias, 29% CIN III and 7% CIN II. Analyzing the positive invasive neoplasias, 6 of 9 (66%) of the fingerprint results were obtained when an HPV primer was paired with an Alu primer. Interestingly, 100% of Alu primed fingerprint results obtained were derived from samples presenting invasive neoplasia (P < 0.025 by chi square).
Mol Cell Probes 1996 Apr
PMID:Use of the polymerase chain reaction to specifically amplify integrated HPV-16 DNA by virtue of its linkage to interspersed repetitive DNA. 873 94

The possible causal association of human papilloma virus (HPV) with transitional cell carcinoma (TCC) of the urinary bladder in Israeli Jewish patients was assessed. One hundred and ten histopathological TCC sections were examined by peroxidase anti-peroxidase (PAP) method. HPV capsid antigen was demonstrated in 19 out of 110 cases (17.3%). HPV-DNA sequences, determined by in situ DNA-DNA hybridization at high stringency wash were present in 24 cases (21.8%): 16(14.5%) cases proved to be HPV6/11 and 8 (7.3%) were HPV 16/18 positive. Four (3.6%) of the HPV 6/11 positive specimens cross hybridized with HPV 31/33/35 at low stringency conditions. Sixteen samples known to be positive by in situ hybridization were reconfirmed by polymerase chain reaction (PCR). When the PCR was performed on the 43 negative cases, an additional 4(9.3%) HPV positive cases were revealed: two proved to be HPV 6/11 and two HPV 16/18. Comparison of the different methods for HPV detection in 59 TCC histopathological samples, showed good correlation; an overall positivity of 33.9% by PCR, 27.1% by in situ hybridization and 25.4% by PAP was observed. Forty one samples from nontumoral material of the bladder or post mortem specimens served as controls and 4.8% HPV DNA was present in only two cases: one HPV 6/11 and one 16/18. Hence, HPV in TCC of the bladder is detected at a relatively high frequency and might be involved in the pathogenesis of this tumor among Jewish population in Israel.
Cell Mol Biol (Noisy-le-grand) 1995 Dec
PMID:Presence of human papilloma virus in transitional cell carcinoma in Jewish population in Israel. 874 82

Normal human cells in culture become senescent after a limited number of population doublings. Senescent cells display characteristic changes in gene expression, among which is a repression of the ability to induce the c-fos gene. We have proposed a two-stage model for cellular senescence in which the mortality stage 1 (M1) mechanism can be overcome by agents that bind both the product of the retinoblastoma susceptibility gene (pRB)-like pocket proteins and p53. In this study we determined whether the repression of c-fos at M1 was downstream of the p53 or pRB-like "arms" of the M1 mechanism. We examined c-fos expression during the entire lifespan of normal human fibroblasts carrying E6 (which binds p53), E7 (which binds pRB), or both E6 and E7 of human papilloma virus type 16. The results indicate a dramatic change in cellular physiology at M1. Before M1, c-fos inducibility is controlled by an E6-independent mechanism that is blocked by E7. After M1, c-fos inducibility becomes dependent on E6 whereas E7 has no effect. In addition, a novel oscillation of c-fos expression with an approximately 2-h periodicity appears in E6-expressing fibroblasts post-M1. Accompanying this shift at M1 is a dramatic change in the ability to divide in low serum. Before M1, E6-expressing fibroblasts growth arrest in 0.3% serum, although they continue dividing under those conditions post-M1. These results demonstrate the unique physiology of fibroblasts during the extended lifespan between M1 and M2 and suggest that p53 might participate in the process that represses the c-fos gene at the onset of cellular senescence.
Mol Biol Cell 1996 Jun
PMID:Age-dependent alterations of c-fos and growth regulation in human fibroblasts expressing the HPV16 E6 protein. 881 2


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