Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity.
BACKGROUND
Prostate cancer is the most common noncutaneous male cancer and one of the least understood malignant diseases. Identifying key genetic factors involved in the metastasis of prostate cancer cells is critical. In this study, we used selective subtractive differential gene display to identify a gene whose decreased expression may contribute to the growth and expansion of prostate cancer.


METHODS
We used 192 primer pair combinations and polymerase chain reaction technology to identify genes expressed in the benign prostate cell line PNT-2 but not in the malignant prostate cancer cell lines LNCaP, Du-145, PC-3, or PC-3M. The tazarotene-induced gene 1 (TIG1) was chosen for further study. TIG1 expression in normal tissues and cell lines was analyzed by northern blot and in normal and tumor prostate tissue sections by in situ hybridization. The in vitro invasiveness (migration through extracellular matrix) and in vivo tumorigenicity (growth in nude mice) were assessed for the highly malignant PC-3M cell line transfected with TIG1 or control cDNA. All statistical tests were two-sided.


RESULTS
TIG1 mRNA was expressed in a variety of normal tissues other than prostate tissue. TIG1 mRNA was detected in all 10 normal human prostate tissues and all 51 benign prostatic hyperplastic tissues analyzed but in only four of 51 malignant prostate tissues analyzed. Compared with vector-transfected cells, transfection of PC-3M cells with TIG1 decreased in vitro invasiveness from 14.7% to 3.7%, (mean difference = 11%; 95% confidence interval [CI] = 9.2% to 12.8%, P<.001) and decreased in vivo tumorigenicity from an average tumor weight of 1.31 g to 0.55 g, (mean difference = 0.76 g; 95% CI = 0.43 to 1.09 g, P<.001).


CONCLUSIONS
TIG1 may be a tumor suppressor gene whose diminished expression is involved in the malignant progression of prostate cancer.
Jing
Chun
C
Department of Pathology, Faculty of Medicine, University of Liverpool, UK.
El-Ghany
Manal Abd
MA
Beesley
Carol
C
Foster
Christopher S
CS
Rudland
Philip S
PS
Smith
Paul
P
Ke
Youqiang
Y
D000595:Amino Acid Sequence; D000818:Animals; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009539:Nicotinic Acids / Q000235:genetics* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012176:Retinoids / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D009539:Nicotinic Acids; D011506:Proteins; C452562:RARRES1 protein, human; D012333:RNA, Messenger; D012176:Retinoids