Novel expressed sequences identified in a model of androgen independent prostate cancer.
BACKGROUND
Prostate cancer is the most frequently diagnosed cancer in American men, and few effective treatment options are available to patients who develop hormone-refractory prostate cancer. The molecular changes that occur to allow prostate cells to proliferate in the absence of androgens are not fully understood.


RESULTS
Subtractive hybridization experiments performed with samples from an in vivo model of hormonal progression identified 25 expressed sequences representing novel human transcripts. Intriguingly, these 25 sequences have small open-reading frames and are not highly conserved through evolution, suggesting many of these novel expressed sequences may be derived from untranslated regions of novel transcripts or from non-coding transcripts. Examination of a large metalibrary of human Serial Analysis of Gene Expression (SAGE) tags demonstrated that only three of these novel sequences had been previously detected. RT-PCR experiments confirmed that the 6 sequences tested were expressed in specific human tissues, as well as in clinical samples of prostate cancer. Further RT-PCR experiments for five of these fragments indicated they originated from large untranslated regions of unannotated transcripts.


CONCLUSIONS
This study underlines the value of using complementary techniques in the annotation of the human genome. The tissue-specific expression of 4 of the 6 clones tested indicates the expression of these novel transcripts is tightly regulated, and future work will determine the possible role(s) these novel transcripts may play in the progression of prostate cancer.
Quayle
Steven N
SN
Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 4E6, Canada. squayle@bccrc.ca <squayle@bccrc.ca>
Hare
Heidi
H
Delaney
Allen D
AD
Hirst
Martin
M
Hwang
Dorothy
D
Schein
Jacqueline E
JE
Jones
Steven J M
SJ
Marra
Marco A
MA
Sadar
Marianne D
MD
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D020506:Untranslated Regions
D000728:Androgens; D012333:RNA, Messenger; D020506:Untranslated Regions