Expression changes of CAV1 and EZH2, located on 7q31 approximately q36, are rarely related to genomic alterations in primary prostate carcinoma.
The chromosomal region 7q was repeatedly found to be rearranged in prostate carcinoma. It harbors several well described candidate tumor suppressor and oncogenes. We addressed two genes with opposite roles in cancer; CAV1, a putative tumor suppressor gene at 7q31, and EZH2 at 7q36, which is believed to promote tumor progression. Our primary aim was to assess their expression changes in primary tumors, and then to elucidate the underlying mechanism, assuming that genomic alterations of either locus could affect the other gene as well. In 35 prostate tumor samples, compared with adjacent tissues, CAV1 was overall downregulated (P < 10(-06)), whereas EZH2 was significantly overexpressed (P < 10(-06)). The observed dysregulations were coincident in nearly 70% of the cases. Copy number changes occurred in few tumors. Loss of CAV1 DNA was only marginally associated with reduced expression (P = 0.07), however, and genomic amplification of EZH2 could not explain its upregulation. Through bisulfite sequencing of four tumor samples, CpG-hypermethylation was verified as an alternative mechanism for CAV1 silencing, as reported previously. Moreover, it could also be involved in the reactivation of EZH2.
Bachmann
Natascha
N
Department of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Haeusler
Juergen
J
Luedeke
Manuel
M
Kuefer
Rainer
R
Perner
Sven
S
Assum
Guenter
G
Paiss
Thomas
T
Hoegel
Josef
J
Vogel
Walther
W
Maier
Christiane
C
D051242:Caveolin 1 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
C495540:CAV1 protein, human; D051242:Caveolin 1; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2