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

During Drosophila hindgut development, bowl, caudal/CDX, brachyenteron/Brachyury/TBX, fork head/FOX, drumstick, lines, and wingless/WNT play important roles. Drosophila bowl gene is homologous to Drosophila odd-skipped (odd) gene and odd-skipped related gene (sob). Here, human OSR1, related to Drosophila odd, was isolated using bioinformatics and cDNA-PCR. OSR1 was found to encode 266 amino-acid protein with three C2H2-type zinc fingers, a tyrosine phosphorylation site (Tyr 203), and several putative PXXP SH3 binding motifs. Three zinc fingers and a tyrosine phosphorylation site were conserved among human OSR1, OSR2, Drosophila odd, sob, and bowl. OSR1 showed 63.6% total amino-acid identity with OSR2. OSR1 gene consisting of three exons was located on human chromosome 2p24. OSR1 mRNA of 2.3-kb in size was detected in adult colon, small intestine, prostate, testis, and fetal lung. OSR1 mRNA was significantly up-regulated in a pancreatic cancer cell line MIA PaCa-2, and was weakly expressed in gastric cancer cell lines OKAJIMA, MKN45, pancreatic cancer cell lines PANC-1, BxPC-3, AsPC-1, PSN-1, Hs766T, and esophageal cancer cell line TE10. Among 10 cases of primary gastric cancer, OSR1 mRNA was up-regulated in 5 cases, and was down-regulated in 2 cases. This is the first report on molecular cloning and characterization of human OSR1.
Int J Mol Med 2002 Aug
PMID:Molecular cloning and characterization of OSR1 on human chromosome 2p24. 1211 63

Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor (VDR) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX-2, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX-2, Fok1, and Taq1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX-2 GA and AA (odds ratios [OR] = 2.11 and 2.02, respectively) and Fok1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX-2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 combinations, FFTT (P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two- or three-genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure.
Environ Mol Mutagen 2004
PMID:Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer. 1499 52

We have used chromatin immunoprecipitation (ChIP) assay to follow transcription factor loading and monitor changes in covalent histone modifications associated with the prostate-specific antigen and kallikrein (KLK2) genes in response to androgen and antiandrogen in LNCaP cells. The dynamics of testosterone (T)-induced loading of androgen receptor (AR) onto the proximal promoters of the genes differed significantly from that onto the distal enhancers. Significantly more holo-AR was loaded onto the enhancers than the promoters, but the receptor's residence time was more transient on the enhancers. Even though holo-AR recruited some RNA polymerase II (Pol II) onto the enhancers, the principal Pol II transcription complex was assembled on the promoters. The pure antiandrogen bicalutamide (CDX) complexed to AR elicited occupancy of the prostate-specific antigen promoter, but not that of the enhancer, whereas the partial antagonists cyproterone acetate (CPA) and mifepristone (RU486) were capable of promoting AR loading also onto the enhancer. In contrast to the CDX-occupied receptor, both CPA- and RU486-bound AR recruited Pol II and coactivators p300 and glucocorticoid receptor-interacting protein 1 (GRIP1) onto the promoter and enhancer. However, CPA and RU486 also brought about a simultaneous recruitment of the nuclear receptor corepressor (NCOR) onto the promoter as efficiently as CDX. There were dynamic changes in covalent modifications of histone H3: acetylation of lysine 9 and 14, methylation of arginine 17, phosphorylation of serine 10 as well as di- and tri-methylation at lysine 4 of the H3 N-terminal tail were enhanced in response to T, but not after CDX treatment. Collectively, these results indicate that transcriptional activation by AR is accompanied by a cascade of distinct covalent histone modifications and that the pure antiandrogen CDX and the partial antagonists CPA and RU486 exhibit clear differences in their ability to promote recruitment of histone-acetylating and histone-deacetylating complexes in human prostate cancer cells.
Mol Endocrinol 2004 Nov
PMID:Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. 1530 89

Primary and secondary mucinous tumors can involve the ovaries and have similar histologic appearances. The differential diagnosis is important for surgical and chemotherapeutic treatment and for the prognosis, but often it is extremely difficult. This article discusses an immunohistochemical panel that includes carcinoembryonic antigen (CEA), cytokeratin (CK) 7, CK20, CA125, CA19.9, and a new marker, CDX-2, for the distinction between primary ovarian mucinous carcinomas and metastatic (intestinal) ovarian tumors. Forty-three cases representing primary and secondary ovarian tumors were considered and consisted of 14 primary mucinous ovarian carcinomas (PMOCs) and 29 secondary (intestinal) ovarian tumors (SIOTs). Fisher exact test was performed to evaluate the reliability of the respective antibodies to discriminate between PMOCs and SIOTs. CDX-2 was diffusely positive in all SIOTs and was expressed focally in 3 cases (21.42%) of PMOCs. CK7 was diffusely positive in 13 cases (44.82%) of SIOTs and in 13 cases (92.85%) of PMOCs. CK20 was diffusely positive in 17 cases (58.62%) of SIOTs and in 6 cases (42.85%) of PMOCs. CEA was diffusely positive in 28 cases (96.55%) of SlOTs and in 12 cases (85.71%) of PMOCs. CA 19.9 was positive in all SIOTs and in 12 cases (85.71%) of PMOCs. CA125 was positive in 3 cases (10.34%) of SIOTs and in 4 cases (28.57%) of PMOCs. CK7 and especially CDX-2, a specific and sensitive marker, can aid pathologists in making a differential diagnosis (P = 0.003 and P < 0.0005, respectively), whereas CEA, CK20, CA125, and CA 19.9 markers are not high enough to distinguish between primary and secondary mucinous ovarian tumors.
Appl Immunohistochem Mol Morphol 2004 Jun
PMID:Utility of CDX-2 in distinguishing between primary and secondary (intestinal) mucinous ovarian carcinoma: an immunohistochemical comparison of 43 cases. 1535 37

Extramammary Paget's disease (EMPD) is a rare condition whose importance is amplified by its association with either cutaneous or internal malignancy. Recently it has been shown that EMPD is not a single disease but can be divided into cutaneous and endodermal subtypes. The authors studied 12 new cases of immunohistochemically well-characterized EMPD, including HER-2/neu and CDX-2 immunophenotyping. The latter represents a novel application of this nuclear transcription factor, considered to be a relatively specific IHC marker for gastrointestinal-type epithelium. Cutaneous EMPD, accounting for 10 of the 12 (83%) cases, was CDX2-/HER2+; endodermal EMPD, accounting for 2 of the 12 (17%) cases, was CDX2+/HER2-. Four of the 12 cases (33%) were associated with a malignancy (two cutaneous adenocarcinomas, two colorectal carcinomas). The two cases of cutaneous adenocarcinoma occurred in the cutaneous group (2/10 [20%]), while the two cases of rectal carcinoma (one invasive, one in situ) occurred in the endodermal group (2/2 [100%]). Since EMPD subtypes have specific implications with regard to cancer risk, immunophenotyping should be performed in all cases. CDX-2 immunoreactivity may be useful in the subtyping of EMPD.
Appl Immunohistochem Mol Morphol 2005 Dec
PMID:Potential diagnostic utility of CDX-2 immunophenotyping in extramammary Paget's disease. 1628 Jun 63

Distinguishing between primary adenocarcinomas and secondary colonic adenocarcinomas of the urinary bladder is often difficult because they appear morphologically similar but invariably require different treatment strategies. The aim of the study was to define the utility of a limited immunohistochemical panel consisting of CDX-2, cytokeratins 7 (CK7) and 20 (CK20), and carcinoembryonic antigen (CEA) in differentiating primary from secondary bladder adenocarcinomas. Formalin-fixed, paraffin-embedded tissues from 8 primary bladder adenocarcinomas and 23 colorectal adenocarcinomas involving the bladder were included in the study. Statistical analysis was performed using the Fisher exact test. The majority (87.5%) of primary bladder adenocarcinomas were CDX-2 negative, and only one case of primary bladder adenocarcinoma was positive, while CDX-2 was strongly expressed in the nucleus of all cases of secondary (colonic) bladder tumor (P < 0.0005). Five cases (62.5%) of primary bladder adenocarcinoma and one case (4.3%) of secondary bladder tumor showed positive staining for CK7 (P = 0.002), whereas CK20 showed positive staining in five cases (62.5%) of primary bladder adenocarcinoma and in all the secondary bladder tumors (P = 0.012). All 23 secondary bladder tumors and 7 primary bladder adenocarcinomas (87.5%) expressed CEA (P = 0.25). These data demonstrate that a restricted immunohistochemical panel consisting of CDX-2, CK7, CK20, and CEA may be of use in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.
Appl Immunohistochem Mol Morphol 2005 Dec
PMID:Immunohistochemistry in the differential diagnosis between primary and secondary intestinal adenocarcinoma of the urinary bladder. 1628 Jun 66

The ulcer-associated cell lineage (UACL) induced at the site of ileac chronic ulceration in Crohn's disease has been reported to show histological differentiation resembling gastric pyloric mucosa. To clarify the significance of homeobox gene-encoded transcription factors in the formation of the UACL in Crohn's disease, we investigated the immunohistochemical expression of gastrointestinal mucins (MUC5AC for gastric surface mucous cells; MUC6 for gastric gland mucous cells, and MUC2 for intestinal goblet cells) and homeobox gene-encoded transcription factors (CDX-2 for intestinal mucosa and PDX-1 for pyloric mucosa) in the UACL. The analysis was undertaken on ileal mucosa obtained from ileal resections performed in 19 patients with active Crohn's disease of the small bowel. The UACL was observed in nine patients. In the UACL, expression of mucous cells with a foveolar-structure showed immunoreactivity to MUC5AC, and the mucous cells with a glandular structure showed immunoreactivity to MUC6, and the expression of MUC2 was decreased. In addition, we detected the decreased expression of CDX-2 along with the increased expression of PDX-1 in the UACL. The UACL showed histological differentiation simulating gastric pylori mucosa. The down-regulation of CDX-2 and the up-regulation of PDX-1 could be an important mechanism in the induction of the UACL.
J Mol Histol 2008 Apr
PMID:Altered expression of CDX-2, PDX-1 and mucin core proteins in "Ulcer-associated cell lineage (UACL)" in Crohn's disease. 1795 87

Histomorphologic features and routine endocrine immunohistochemical (IHC) markers do not differentiate neuroendocrine tumors (NETs) in relation to their location, making it difficult to establish the site of origin of a metastatic neoplasm. Site-specific markers would be useful, particularly when examining small biopsies. CDX-2 and thyroid transcription factor-1 (TTF-1) are transcription factors that have been recently proposed as IHC markers of intestinal and pulmonary adenocarcinomas, respectively. However, their expression in NETs has not been widely studied. The objective of this study is to evaluate the expression of TTF-1 and CDX-2 in NETs and their potential usefulness in distinguishing gastrointestinal and pulmonary NETs from other sites. We performed an IHC study on formalin-fixed, paraffin-embedded sections from 155 primary NETs, including 60 pulmonary, 60 gastrointestinal, 30 pancreatic, and 5 NETs from other sites. In addition, we evaluated 13 metastatic NETs, including 11 cases of gastrointestinal and 2 of pulmonary origin. In this study, CDX-2 was expressed in 28/60 (47%) of gastrointestinal NETs with the following results: 11/11 (100%) appendiceal, 12/14 (86%) small intestinal, 3/4 (75%) colonic, 2/11 (18%) rectal, and 0/20 (0%) gastric. TTF-1 was expressed in pulmonary carcinoid tumors in 13/30 (43%) and in 27/30 (90%) pulmonary small cell carcinomas. NETs of other origins (pancreas, skin, ovary, and thymus) were negative for both TTF-1 and CDX-2. Metastatic neuroendocrine neoplasms of intestinal origin were positive for CDX-2 and negative for TTF-1. In conclusion, CDX-2 expression is highly specific in identifying NETs of intestinal origin and TTF-1 expression is helpful in identifying NETs of pulmonary origin, which can be quite useful in the diagnosis of metastatic NETs of unknown origin.
Appl Immunohistochem Mol Morphol 2007 Dec
PMID:Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. 1809 83

Ovarian mucinous neoplasm (OMN) is traditionally classified as either intestinal type or endocervical-like subtypes. The 2 subtypes represent different clinicopathologic characteristics. The immunophenotype of the 2 subtypes has not been adequately investigated. In this study, we investigated 14 intestinal type OMNs (borderline and adenocarcinoma) and 12 endocervical-like OMNs (borderline and adenocarcinoma) for their expression of PDX-1, CDX-2, CA-125, CK7, CK20, WT-1, D2-40, and TTF-1. We also included 15 colorectal adenocarcinomas metastatic in the ovary, as they may occasionally mimic OMN. The intestinal type OMNs were positive for PDX-1 (100%), CK7 (100%), CK20 (100%), CDX-2 (29%), whereas were negative for CA-125. The endocervical-like OMNs were positive for CA-125 (100%) and CK7 (100%), whereas were negative for CK20, PDX-1, and CDX-2. Metastatic colorectal adenocarcinomas were positive for CK20 (100%), CDX-2 (100%), and PDX-1 (33%), whereas were negative for CA-125 and CK7. All of the intestinal type and endocervical-like OMNs as well as metastatic colorectal adenocarcinomas were negative for WT-1, D2-40, and TTF-1. Our results demonstrated that the intestinal type and endocervical-like OMNs are immunophenotypically distinct entities. The 2 subtypes can be separated from metastatic colorectal adenocarcinoma by the different immunohistochemical profile of PDX-1, CA-125, CK7, CK20, and CDX-2. In the work-up of mucinous adenocarcinoma in the ovary or abdominal cavity, caution should be exercised in interpreting the possible primary site on the basis of the immunohistochemical profiles.
Appl Immunohistochem Mol Morphol 2008 Oct
PMID:Intestinal type and endocervical-like ovarian mucinous neoplasms are immunophenotypically distinct entities. 1866 37

In this paper, we describe the development of a novel rabbit monoclonal cytokeratin 7 (CK7) antibody. CK7 is widely used in immunohistochemical tests that are commonly performed in histopathology laboratories. Rabbits were immunized with a peptide corresponding to C-terminus of CK7. Recombinant monoclonal antibodies were developed using proprietary technology. Antibodies were screened by enzyme-linked immunosorbent assay against CK7 peptide, and the specificity of the antibody was verified by Western blotting on Hela cell lysates and by immunohistochemical staining on formalin-fixed paraffin-embedded tissue sections. One clone, designated as BC1 was selected and tested on a variety of human tissues. Its reactivity was tested and compared with a well-characterized mouse monoclonal CK7 antibody OV-TL 12/30 on lung, breast, ovarian, and colon cancers, and on a variety of normal tissues. The staining patterns and specificity were concordant with mouse monoclonal OV-TL 12/30. The BC1 clone, however, showed superior staining to OV-TL 12/30 in terms of intensity and staining of debris. CK7 combined with CK20 or CDX2 and TTF1 is a common panel used in histopathology laboratories in discrimination between primary adenocarcinomas and metastatic lung adenocarcinomas from colonic origin. We then developed a 4-step double stain (multiplex) assay by combining CDX-2 with CK7 in an antibody cocktail and tested the efficacy on lung, breast, and colon cancers. Results showed that this novel antibody can be used as a single component and/or in combination with CDX2 and TTF1 in applications for diagnostic pathology.
Appl Immunohistochem Mol Morphol 2009 May
PMID:Characterization and applications of a newly developed rabbit monoclonal antibody to cytokeratin 7 (CK7) for immunohistochemistry. 1909 79


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