Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the CD44 variant (CD44v) isoforms on the cell surface have been correlated with tumor metastasis. In this study we have examined the expression of CD44 variant isoforms in human breast carcinoma samples by a variety of techniques including immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and nucleotide sequencing. Using RT-PCR, we have determined that normal human breast tissue contains primarily the CD44 epithelial (CD44E) form and very little CD44 standard (CD44s) form. However, metastatic breast carcinomas appear to overexpress both the CD44E and CD44s forms and also display multiple new species of CD44 variant isoforms. Histocytochemical staining using anti-CD44 antibody (recognizing a common determinant of the CD44 class of glycoproteins) confirms that the CD44 molecules are overexpressed and preferentially located in metastatic breast cancer tissues. Nucleotide sequencing analyses indicate that at least four new CD44 variant isoforms (i.e., displaying unique splicing via the insertion or the deletion of exons 7, 10, 11, and 14) may be closely associated with human metastatic breast cancers. These newly described CD44 variant isoforms may be useful for monitoring the progression of human breast cancer metastasis.
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PMID:New CD44 splice variants associated with human breast cancers. 752 35

The cell-surface receptor for hyaluronic acid, CD44, is expressed by both normal and malignant cells. Numerous CD44 isoforms have recently been identified that are derived by alternative ribonucleic acid splicing. The expression of some CD44 isoforms has been shown to be involved in tumor progression and metastatic spread in a rat carcinoma model and in human carcinomas. In the present study, CD44 isoform expression was evaluated by reverse transcriptase-polymerase chain reaction (PCR) analysis in frozen sections derived from three samples of normal brain tissue and from 40 brain tumors, including samples of glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, cerebral primitive neuroectodermal tumor, medulloblastoma, metastatic colon carcinoma, and metastatic melanoma. Normal brain tissue adjacent to the tumors was also examined in 14 of 18 glioblastomas. In all normal brain and tumor samples, with the exception of metastases from colon carcinoma, PCR analysis demonstrated one prominent product that corresponded to the CD44H hematopoietic form of CD44. Metastases from colon carcinoma demonstrated two prominent PCR amplification products corresponding to CD44H and CD44R1. These results suggest that CD44H is the predominant isoform of this protein in normal human brain tissue and in human neuroectodermal tumors of varying degrees of malignancy. The ability of CD44H to mediate tumor cell motility and invasiveness (in contrast to CD44R1) suggests that the CD44 alternative splicing pattern of neuroectoderm-derived tumors may enhance their local biological aggressiveness and intracerebral spread. The lack of expression of larger molecular weight CD44 variants by primary brain tumors may also partially explain why these tumors rarely metastasize to distant sites.
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PMID:Alternative RNA splicing of the hyaluronic acid receptor CD44 in the normal human brain and in brain tumors. 753 36

Isoforms of the transmembrane glycoprotein CD44, generated by alternative RNA splicing, have been correlated to tumor dissemination. For evaluation of the potential role of CD44 variant isoforms in non-Hodgkin's lymphoma (NHL), the presence of CD44 isoforms was analyzed in a large panel of reactive and neoplastic lymphoid tissues by immunohistochemical staining, as well as detection of CD44 variant RNAs by the reverse transcriptase-polymerase chain reaction. Whereas the CD44 standard or hematopoietic isoform (CD44s), devoid of the variant regions, was expressed in all leukocyte subpopulations, the variant isoforms (CD44v) showed a highly restricted pattern of expression, mainly observed in epithelial layers of lymphoid tissues and subpopulations of leukocytes after stimulation. In addition to a strong expression of CD44s, variant isoforms containing CD44-6v in combination with other variant exons were observed predominantly in aggressive lymphoma and were associated with a shorter overall survival of patients (n = 138; P < .0001). Moreover, multivariate analysis indicated CD44-6v as a new independent prognostic parameter in high grade NHL in comparison with the risk groups defined by the International NHL Lymphoma Prognostic Factors Project (N Engl J Med 329:987, 1993).
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PMID:CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor. 753 83

CD44 is a glycosylated adhesion molecule which may undergo alternative splicing of 10 possible exons to generate variant isoforms. A number of CD44 variant isoforms expressed by tumor cells have been correlated with metastatic and proliferative behavior. In this study, we have characterized CD44 isoform expression on three prostate cancer cell lines: ALVA-31, PPC-1, and LNCaP. Using reverse transcriptase-polymerase chain reaction, we have found that ALVA-31 and PPC-1 cells express multiple CD44 isoforms, including CD44s (standard form), CD44E (epithelial form), and an exon 14-containing form. In addition, two smaller forms have been detected: one using an alternative donor splice site within exon 5, and a novel form omitting exon 5 entirely. The CD44 isoforms expressed by ALVA-31 and PPC-1 cells appear to be preferentially located on the cell surface. By contrast, LNCaP cells do not express any of the CD44 forms at the RNA or protein level. Both PPC-1 and ALVA-31 cells display tumorigenesis and invasiveness in nude mice, whereas LNCap cells exhibit a less malignant phenotype, suggesting a correlation between CD44 variant (CD44v) expression and aggressive prostate tumor behavior. Functional characterization reveals that CD44 mediates prostate cell adhesion to extracellular hyaluronic acid (HA). In addition, the CD44 cytoplasmic domain binds specifically to ankyrin, a membrane cytoskeletal protein. Double immunofluorescence labeling and confocal microscopic analyses indicate that HA binding induces the HA receptor (i.e., CD44) to form capped structures. Importantly, intracellular ankyrin is preferentially accumulated underneath HA receptor-capped structures. These results suggest that cytoskeletal proteins such as ankyrin are closely associated with CD44-mediated signaling events induced by HA. Finally, HA-mediated transmembrane interactions between CD44 isoforms and cytoskeletal proteins (i.e. ankyrin) may play a pivotal role in regulating tumor cell behavior during human prostate cancer development.
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PMID:Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells. 754 57

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.
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PMID:Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors. 754 38

To examine whether renal cell carcinoma display altered CD44 expression we performed reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CD44 in the tissues resected from 19 patients with renal cell carcinoma and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT-PCR Southern blot method reported by Matsumura et al. In 12 of 17 (70.6%) cases, about a 700 base pairs band was emphasized in cancerous tissues compared with normal kidney. Moreover, we found that this isoform is the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 variants sharing exon v10. Our findings suggest that this variant form plays some roles in renal cell carcinoma.
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PMID:[Expression of CD44 variant form in human renal cell carcinoma]. 763 12

CD44 is a cell surface adhesion molecule postulated to control lymphocyte recirculation by facilitating entry into lymphoid tissue. Tumour cells transfected to overexpress the epithelial variant CD44R1 readily gain access to lymph nodes and distant metastatic sites in animal models, possibly by mimicking circulating lymphocytes. To investigate if human tumours display altered CD44 expression we performed reverse transcriptase a polymerase chain reaction (PCR) analysis of CD44 in 49 specimens from normal colonic mucosa, primary colon and rectal tumours, normal liver, and metastases of 20 patients. The haematopoietic variant CD44H was the principal isoform amplified in all of the specimens, However, 12/14 primary tumours and 16/16 metastatic potential. Moreover, the relative increase with only 2 of 13 normal mucosa specimens. This increase in CD44R1 relative to CD44H expressed by human colon carcinoma cells may increase their metastatic potential. Moreover, the relative increase in PCR amplification of CD44R1 compared with that of CD44H may provide a sensitive method for detecting primary and metastatic colon carcinoma cells in small biopsy specimens.
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PMID:Expression of CD44R1 adhesion molecule in colon carcinomas and metastases. 809 28

CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 variant isoforms were detected. There was a significant increase in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44 isoform expression correlated with grading; ie, no CD44 expression was detected in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more aggressive phenotype to renal cell tumors.
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PMID:Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation. 857 8

The CD44 is a cell adhesion molecule that is present as numerous isoforms created by mRNA alternative splicing. A variety of human carcinomas display the overexpression of CD44 variant isoforms. To identify the relationship between the expression of CD44 variant isoforms and the metastatic potential of colon carcinomas, we performed a polymerase chain reaction analysis following reverse transcriptase treatment for CD44 expression in fresh surgical specimens obtained from 25 colon carcinomas and corresponding normal colonic mucosa. The CD44H, a common type of the CD44 isoform, was amplified from all carcinomas and normal tissues, whereas a splice variant form corresponding to CD44E was expressed in 19 out of 23 colon carcinomas (83%) and 7 out of 19 normal mucosa specimens (37%), suggesting that the CD44E expression was predominantly observed in colon carcinomas compared to normal tissues (p < 0.05). The multivariant form of CD44 was identified in 10 out of 23 carcinomas (44%) and 5 out of 19 normal samples (26%). The CD44E/CD44H (E/H) ratio was significantly higher in colon carcinomas than in normal mucosa (p < 0.01). However, neither the E/H ratio nor CD44 multivariant expression correlated with the clinicopathological features. These results suggest that CD44E expression and high E/H ratio are commonly observed in colon carcinomas and that the expression of the CD44 multivariants is not associated with clinicopathological parameters.
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PMID:[Expression of CD44 variant isoforms in human primary colon carcinomas and metastasis]. 867 63

The CD44 cell adhesion molecule is a surface glycoprotein mainly expressed in lymphoid tissues. Recently, abnormal variants of CD44 including alternatively-spliced large molecular variants, have been reported in many neoplastic tissues. We studied the variation in the size of CD44 molecules in 25 transitional cell carcinomas and 11 normal transitional epithelial tissues, using the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by electrophoresis and Southern blot hybridization. Whereas 23 of 25 (92.0%) tumor tissues expressed CD44 splice variants with large molecular size, only 1 of 11 (9.1%) normal tissues expressed the abnormal variants. Urine sediments from 5 of 7 (71.4%) patients also was positive for the CD44 splice variants. CD44 splice variants are increased markedly in human transitional cell carcinoma. In conclusion, detection of CD44 splice variants using the RT-PCR, which is a convenient molecular biological technique, may be useful in combination with other diagnostic methods such as cytology, flow cytometry, and tumor antigens.
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PMID:Expression of CD44 splice variants in human transitional cell carcinoma. 874 26


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