Characterization of frequently deleted 6q locus in prostate cancer.
The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of 6qTSG transcripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted.
Sun
Mei
M
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, Maryland 20832, USA.
Srikantan
Vasantha
V
Ma
Lanfeng
L
Li
Jia
J
Zhang
Wei
W
Petrovics
Gyorgy
G
Makarem
Mazen
M
Strovel
Jeffrey W
JW
Horrigan
Stephen G
SG
Augustus
Meena
M
Sesterhenn
Isabell A
IA
Moul
Judd W
JW
Chandrasekharappa
Settara
S
Zou
Zhiqiang
Z
Srivastava
Shiv
S
D017209:Apoptosis; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003979:Diazonium Compounds; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*
C504881:4-carboxyl-2,6-dinitrobenzenediazonium ion; D003979:Diazonium Compounds; D005819:Genetic Markers