Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue anoxia occurs early in wound healing. This is accompanied by production of lactate followed by increased hyaluronan and CD44 expression, suggesting a cause and effect relationship. Fibroblasts increased hyaluronan and CD44 when lactate was added to cultures. Increased deposition of hyaluronan correlates with greater turnover. In current models of hyaluronan catabolism, it is tethered to cell surfaces by CD44 in caveolin-enriched invaginations. It is cleaved to 20-kDa fragments by Hyal-2 on the plasma membrane, endocytosed, and delivered ultimately to lysosomes, and further digested by Hyal-1. Sequence analyses of promoter regions of genes for CD44, caveolin-1, Hyal-1, and -2 revealed multiple AP-1 and ets-1 response elements. To test their relevance, RNA from lactate-treated fibroblasts was analyzed by reverse transcriptase-polymerase chain reaction. Increased transcripts of c-fos, c-jun, c-ets, Hyal-1, -2, CD44, and caveolin-1 mRNAs were observed. We have thus identified lactate-activated genes important in the wound healing responses. Similar responses facilitating tumor progression, the Warburg effect, may share such mechanisms.
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PMID:Lactate-sensitive response elements in genes involved in hyaluronan catabolism. 1273 17

Within tumors there appears to be an intricate balance between hyaluronan (HA) synthesis and degradation where the invading edges display increased HA metabolism. The metabolism of HA has not been characterized in breast cancer cell lines; therefore, this study quantitatively identifies and characterizes the enzymes responsible for the synthesis and degradation of HA while correlating gene expression to cancer cell invasiveness and HA receptor status. In ten well-established breast cancer cell lines, the expression of the genes for each hyaluronan synthase (HAS) and hyaluronidase (Hyal) isoform was quantitated using real-time and reverse transcriptase polymerase chain reaction (PCR). The synthesis and degradation rates of hyaluronan were determined by ELISA, while quantitation of HA receptors, CD44 and RHAMM was performed by comparative Western blotting. The molecular weight of HA synthesized by each HAS isoform and the degradation products of each hyaluronidase were characterized by size exclusion chromatography. It was demonstrated that highly invasive cell lines preferentially expressed the HAS2 and Hyal-2 isoforms, while less invasive cells expressed HAS3 and Hyal-3. There was a correlation between elevated levels of HA synthesis, CD44 expression and cancer cell migration thereby highlighting the pivotal role that HA metabolism plays in the aggressive breast cancer phenotype.
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PMID:The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. 1612