Expression and function of ATIP/MTUS1 in human prostate cancer cell lines.
BACKGROUND
We have previously demonstrated Ang II type 2 (AT(2)-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines.


METHODS
To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT(2)-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [(3)H]thymidine incorporation assays.


RESULTS
The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.


CONCLUSIONS
The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT(2)-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression.
Louis
Simon N S
SN
Clinical Pharmacology and Therapeutics Unit, University of Melbourne, Department of Medicine, Austin Health, Heidelberg, Victoria, Australia.
Chow
Laurie
L
Rezmann
Linda
L
Krezel
Michael A
MA
Catt
Kevin J
KJ
Tikellis
Chris
C
Frauman
Albert G
AG
Louis
William J
WJ
D045744:Cell Line, Tumor; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; C474762:MTUS1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D004815:Epidermal Growth Factor; D013936:Thymidine