Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies

Grabmaier, Karin; Weijert, Mirjam de; Uemura, Hirotsugu; Schalken, Jack A.; Oosterwijk, Egbert

doi:10.1016/s0090-4295(02)01711-9

Cited by 5 publications

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The methylation status of the −74 and −6 CpG sites in the CA9 promoter (located near PR2 and within the TA CG TG CA9 HBS, respectively) has been reported to negatively correlate with CA9 expression in renal cells: the CA9 promoter is hypomethylated in CAIX-positive RCCC cell lines, while showing complete methylation in CAIX-negative cells, including normal kidney tissues [43–46]. Intriguingly, compared with normal kidney tissue, no hypomethylation was observed in primary RCCC: investigated CpG dinucleotides in RCCC as well as in normal kidney tissue were generally completely methylated [46]. …”

Section: Introductionmentioning

confidence: 99%

Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show?

Kaluz

Kaluzová

Liao

et al. 2009

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

180

212

View full text Add to dashboard Cite

SUMMARYTranscriptional activation by hypoxia is mediated by the hypoxia-inducible factor (HIF) via binding to the hypoxia-responsive element (HRE). Hypoxia in solid tumors associates with poorer outcome of the disease and reliable cellular markers of tumor hypoxia would represent a valuable diagnostic marker and a potential therapeutic target. In this category, carbonic anhydrase IX (CAIX) is one of the most promising candidates. Here, we summarize the knowledge about transcriptional regulation of CA9. The HRE is the central regulatory element in the CA9 promoter, whereas other elements are limited to lesser roles of amplification of signals received at the HRE. The analysis of known mechanisms of activation of CA9 reveals the prominent role of the HIF-1 pathway. Experimental paradigms with uncoupled HIF-1α stability and transcriptional activity (pericellular hypoxia, proteasomal inhibitor) provide evidence that CA9 expression monitors transcriptional activity of HIF-1, rather than the abundance of HIF-1α. Furthermore, these paradigms could provide a corollary to some of the apparently discordant cases (CAIX+, HIF-1α−) or (CAIX−, HIF-1α+) observed in vivo. In conclusion, the existing data support the notion that CA9, due to the unique structure of its promoter, is one of the most sensitive endogenous sensors of HIF-1 activity.

show abstract

Section: Introductionmentioning

confidence: 99%