ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix.
Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.
VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Cs-F
CF
Hooi
C
C
Blancher
W
W
Qiu
I M
IM
Revet
L H
LH
Williams
M L
ML
Ciavarella
R L
RL
Anderson
E W
EW
Thompson
A
A
Connor
W A
WA
Phillips
I G
IG
Campbell
D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D017931:DNA Primers; C412123:ST7 protein, human; D025521:Tumor Suppressor Proteins