Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study reports the structure and expression rates of genes of the transforming growth factor-alpha (TGF-alpha) signal transduction pathway (TGF-alpha, epidermal growth factor receptor [EGF-R], jun, myc, and metallothionein [MT]) in 47 specimens of ovarian cancer and 21 nonmalignant tissues. The objective was to establish a direct correlation between the genetic activities and the malignant phenotype of the ovarian cancer. The Southern blot technique identified four samples with myc amplification and two with rearranged EGF-R genes. By using the S1 nuclease assay, the analysis of myc transcription showed a similar use of both promotors. Although the size of the investigated transcripts was unaltered, significant differences in the transcription rates were noticed in malignant tissue probes (using northern blot analysis and RNAase protection assay). The following results of messenger RNA analysis in ovarian cancer were observed: EGF-R, negative in 25%, low in 65%, and strongly positive in 10%; TGF-alpha, negative in 34%, low in 36%, and strongly positive in 30%; myc, negative in 8%, low in 64%, and strongly positive in 28%; jun, negative in 4%, low in 58%, and strong in 38%; and MT, low in 80% and strongly positive in 20%. In most nonmalignant tissues studied, no or only a low expression of TGF-alpha, EGF-R, and myc. was found. A comparison of these messenger RNA results with the clinical data from tumors showed four different subgroups of ovarian carcinomas. The results of chemotherapy were known in 32 cases. Tumors with negative or low expression rates of all investigated genes did not respond to chemotherapy; 13 of 18 tumors with high expression rates did respond. Additional signal transduction chains distinct from the TGF-alpha pathway, however, are likely to influence both the expression and activity of transcription factors and MT.
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PMID:Gene structure and expression analysis of the epidermal growth factor receptor, transforming growth factor-alpha, myc, jun, and metallothionein in human ovarian carcinomas. Classification of malignant phenotypes. 842 34

The role of epithelial-stromal interactions in the progression of human papillomavirus-associated squamous intraepithelial lesions to invasive cervical cancer is poorly understood. Using the Matrigel artificial basement membrane assay as a model of keratinocyte invasion, the effects of selected growth factors on penetration of human papillomavirus 16-immortalized keratinocytes through Matrigel were studied. Also studied in this model were the effects of conditioned media from fibroblast lines derived from normal cervical tissues (normal fibroblasts) and adjacent cervical cancer biopsies (tumor-associated fibroblasts) and from primary keratinocytes. Addition of basic fibroblast growth factor, transforming growth factor-alpha, and hepatocyte growth factor/scatter factor or conditioned media from tumor-associated fibroblasts to the Matrigel resulted in near-doubling of penetration of human papillomavirus 16-immortalized keratinocytes, whereas transforming growth factor-beta, platelet derived growth factor-B, or conditioned media from primary keratinocytes decreased penetration 10-fold. Antibodies to basic fibroblast growth factor abrogated the stimulatory effects of conditioned media from tumor-associated fibroblasts on keratinocyte penetration, whereas antibodies to transforming growth factor-beta abrogated the inhibitory effects of conditioned media from normal fibroblasts on keratinocyte penetration. S1 nuclease protection and enzyme-linked immunosorbent assay showed increased expression of transforming growth factor-beta and decreased expression of basic fibroblast growth factor in normal compared with tumor-associated fibroblasts. Messenger RNA in situ hybridization of five cervical cancer biopsies demonstrated basic fibroblast growth factor expression in stromal cells surrounding nests of invading keratinocytes. Epithelial-stromal interactions mediated by growth factors such as transforming growth factor-beta and basic fibroblast growth factor modulate penetration of human papillomavirus 16-immortalized keratinocytes through Matrigel in vitro and these interactions may also be operative in vivo.
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PMID:Epithelial-stromal interactions modulating penetration of matrigel membranes by HPV 16-immortalized keratinocytes. 934 88