Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several glycosylated macromolecules associated with normal and malignant pancreatic ductal cells have been described. We have generated a monoclonal antibody, LD-B1, by immunizing Balb/c mice with the postmicrosomal extract of fresh human pancreatic ductal carcinoma tissue and used it in this study to characterize the nature of the target antigen. The antigen detected by LD-B1 antibody was purified to homogeneity by affinity chromatography. Enzymatic and biochemical analysis showed it to be a nonsialylated glycoprotein that on Western blotting and immunoprecipitation analyses had an apparent molecular weight of 300-400 kDa. The mobility on gels was not affected by reducing or denaturing conditions. Competitive inhibition assays with various MoAbs and lectins indicated that the epitope recognized by LD-B1 antibody involves the carbohydrate sequence Gal beta 1----3Gal beta 1----3(or 4)GlcNAc beta 1----3Gal. Using a double determinant sandwich ELISA, elevated antigen levels were detected in the sera of 5 of 6 patients with pancreatic carcinoma, 0 of 3 patients with chronic pancreatitis, and 12 of 137 normal controls. These results suggest that patients with pancreatic carcinoma exhibit altered expression of a heavily glycosylated molecule related to a blood group precursor immunodeterminant.
Exp Mol Pathol 1990 Oct
PMID:Biochemical characterization and serological immunoassay of a pancreatic carcinoma-associated antigen defined by monoclonal antibody LD-B1. 170 61

Differential screening of a human epidermal cDNA library led to the isolation of cDNA clones homologous to mRNAs specifically expressed in epidermis but weakly or not expressed in the undifferentiated squamous carcinoma cell line TR146. One of these 'differentiation-specific' cDNA clones, A8, hybridized with a 1.7 kb transcript among RNAs isolated from normal human epidermis, but with several transcripts ranging from 1.4 to 2.1 kb when mRNAs were isolated from cultured keratinocytes. We examined the effects of modulators of epidermal differentiation such as calcium and retinoic acid on the production of these transcripts. Their amount was found to increase in the presence of high calcium concentration, but to decrease in the presence of retinoic acid. These results strongly suggest that A8 messages are up-regulated during epidermal differentiation. The sequence of the 1371 bp of A8 cDNA shows a very high GC content. Because of its homology with the murine loricrin mRNA, A8 is likely to correspond either to the human loricrin or to a related protein.
Mol Biol Rep 1990 Nov
PMID:Isolation of a GC-rich cDNA identifying mRNA present in human epidermis and modulated by calcium and retinoic acid in cultured keratinocytes. Homology with murine loricrin mRNA. 171 17

The met proto-oncogene is a member of the family of tyrosine kinase growth factor receptors. We describe the isolation and characterization of a cDNA clone (pOK) for the met receptor from a gastric carcinoma cell line. This clone differs from the published cDNA clone by the absence of 54 bp predicted to encode 18 amino acids in the extracellular domain. The pOK cDNA corresponds to the most abundant met RNA species of 8 kb expressed in human cell lines and tissue, and we show that there are in fact two 8-kb met receptor tyrosine kinase (RTK) isoforms that are generated by alternative splicing. This newly described met isoform when transiently expressed in COS cells encodes a protein of 190 kDa which corresponds in size to the p190 met alpha beta heterodimer expressed in human cell lines. Furthermore, we show that the 190-kDa product of pOK consists of the 140-kDa met beta subunit associated with the 50-kDa met alpha subunit. This finding suggests that both the alpha and beta met chains are encoded by this construct and confirms the hypothesis that a single chain precursor is cleaved to produce both subunits of met. In contrast, the previously characterized met isoform corresponds to a minor met RNA species and encodes a protein of 170 kDa that is not cleaved yet is processed in a manner that allows cell surface expression. Both met RTK isoforms are autophosphorylated in the in vitro kinase assay. These results suggest that different isoforms of the met RTK may have distinct biological activities.
Mol Cell Biol 1991 Jun
PMID:Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing. 171 22

We found that hydrolysates of poly(A)RNA from Ehrlich ascites carcinoma cells which were transcribed by RNA polymerase III contained an unusual component designated as X. It was part of B2 RNA representing a transcript of B2 retroposon, typical of rodents. The component X possesses a cap-like structure, xPPP5'G, where x has al non-nucleotide structure. About half of all B2 RNAs contained this group at the 5'-end. Previously, Epstein et al. (Epstein P., Reddy R., Henning D., Busch H. parallel J. Biol. Chem. 1980. V. 255. P. 8901-8906) detected a similar structure at the 5'-end of small nuclear U6RNA. Later, Singh and Reddy (Singh R., Reddy R. parallel Proc. Natl. Acad. Sci. USA. 1989. V. 86. P. 8280-8283) showed methyl to be the blocking group in the component X of U6RNA. Besides B2 RNA, we found 5'-ends containing methyl groups in 7S K-RNA.
Mol Biol (Mosk)
PMID:[B2 RNA and 7SK RNA, transcripts of RNA-polymerase III, have a cap-like structure at the 5'-end]. 171 20

A full length human androgen receptor (hAR) cDNA was constructed from cDNA and genomic clones. Structurally the 10.6-kilobase (kb) hAR cDNA consists of a long 5'-untranslated region (5'-UTR, 1.1 kb), a previously described open reading frame (ORF, 2.7 kb) (Trapman, J., Klaassen, P., Kuiper, G. G. J. M., van der Korput, J. A. G. M., Faber, P. W., van Rooij, H. C. J., Geurts van Kessel, A., Voorhorst, M. M., Mulder, E., and Brinkmann, A. O. (1988) Biochem. Biophys. Res. Commun. 153, 241-248; Faber, P. W., Kuiper, G. G. J. M., van Rooij, H. C. J., van der Korput, J. A. G. M., Brinkmann, A. O., and Trapman, J. (1989) Mol. Cell. Endocrinol. 61, 257-262), and a very long 3'-untranslated region (3'-UTR, 6.8 kb). The complete 5'- and 3'-UTRs were found to be encoded by the previously reported first and eight protein coding exons of the hAR gene, respectively (Kuiper, G. G. J. M., Faber, P. W., van Rooij, H. C. J., van der Korput, J. A. G. M., Ris-Stalpers, C., Klaassen, P., Trapman, J., and Brinkmann, A. O. (1989) J. Mol. Endocrinol. 2, R1-R4). Two major sites of transcription initiation were identified in a 13-base pair region. DNA fragments spanning these transcription initiation sites conferred promoter activity upon a promoterless chloramphenicol acetyltransferase reporter gene construct. Two equally effective, functional polyadenylation signals (ATTAAA and CATAAA) at a mutual distance of 221 base pairs were detected. The ATTAAA hexamer sequence gave rise to multiple sites of poly(A) addition, whereas only one position was used following the CATAAA hexamer. In LNCaP prostatic carcinoma cells an alternatively spliced hAR mRNA species was identified which lacks 3 kb of the 3'-UTR.
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PMID:Characterization of the human androgen receptor transcription unit. 171 Feb 13

The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.
Mol Carcinog 1991
PMID:TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis. 171 Apr 62

We have isolated a cDNA clone encoding the human S3 ribosomal protein from a normal human colon cDNA library. The clone was identified as one of many that detected genes whose level of expression was increased in adenocarcinoma of the colon relative to normal colonic mucosa. Increased levels of the S3 transcript were present in the tumors of all eight patients examined. Moreover, the S3 mRNA was also more abundant in 7 of 10 adenomatous polyps, the presumed precursor of carcinoma. Additional studies demonstrated that increased levels of mRNAs encoding several other ribosomal proteins, including S6, S8, S12, L5, and P0, were present in colorectal tumors and polyps. These results suggest that there is increased synthesis of ribosomes in colorectal tumors and that this increase is an early event in colon neoplasia.
Mol Cell Biol 1991 Aug
PMID:Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. 171 97

A transforming activity associated with Chinese nasopharyngeal carcinoma (NPC) cell line CNE2 DNA has been identified by transfer into nontransformed promotion-sensitive mouse JB6(P+) C141 cells. To clone this transformation-associated sequence, we carried out three cycles of transfection, followed by cloning of anchorage-independent transformants in soft agar. A tertiary CNE/JB6 clonal transfectant cell line 625 whose DNA showed transforming activity, as indicated in both soft-agar assay and nude-mice implantation, was used to make a genomic library in the vector lambda dash. Using the human repeated sequence Blur 8 to screen the library, we obtained 10 human Alu-positive clones. A cloned Alu-positive insert of 16 kbp, CNE 323, was characterized in detail. CNE 323 transferred moderate transforming activity when introduced into JB6 P+ cells and showed no homology to Ha-, Ki-, or N-ras genes; human promotion sensitivity genes; src, myb, jun, myc, fos, raf, or int-2 oncogenes; or epidermal growth factor receptor. The isolated CNE 323 DNA sequence appeared to preserve the genomic structure of the original sequence found in CNE2 cells and in nude mouse tumors induced by CNE2 cells or by CNE/JB6 transfectant cells, indicating that the cloned NPC sequence was activated during NPC carcinogenesis and not during transfection or construction of the library, and that the cloned sequence or a larger sequence of which it was part played a role in tumor formation. Finally, we identified a 1.3-kb mRNA that hybridizes to a subclone of the 16-kb NPC sequence in CNE2 cell poly (A)+ RNA.
Mol Carcinog 1991
PMID:Isolation and partial characterization of a transformation-associated sequence from human nasopharyngeal carcinoma. 171 41

The effect of progesterone and nine synthetic progestogens on the activity rate of microsome estrone sulfatase obtained from human breast carcinoma tissues was studied. The progestogens were classified into three groups: group I with a strict inhibitor effect: demegestone and chlormadinone acetate; group II with a strict activator effect: medroxyprogesterone acetate, quingestanol acetate, lynestrenol and progesterone and group III with a nonsignificant effect: dydrogesterone, promegestone, norgestrel and danazol. Demegestone was the most potent inhibitor and medroxyprogesterone acetate and quingestanol acetate had the highest activator effect. The effect of Triton X-100, a nonionic detergent, was also tested. This detergent consistently increased the microsome estrone sulfatase activity. A comparison was made between the effects of demegestone, medroxyprogesterone acetate and danazol on estrone sulfatase activity measured with or without Triton X-100 in the incubation medium. The presence of the detergent modified the progestogen action. Our results suggest that synthetic progestogens can influence the estrone sulfatase activity measured in human breast carcinoma tissues. However, the effect of progestogens was dependent on experimental conditions. Progestogens such as demegestone and chlormadinone acetate which inhibited estrone sulfatase activity in intact preparations, can reduce the intracellular production of biological active estrogen via the sulfatase pathway.
J Steroid Biochem Mol Biol 1991 Dec
PMID:In vitro effect of synthetic progestogens on estrone sulfatase activity in human breast carcinoma. 175 97

Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell.
Mol Cell Endocrinol 1991 Nov
PMID:Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation. 176 Nov 61


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