Maspin expression profile in human prostate cancer (CaP) and in vitro induction of Maspin expression by androgen ablation.
OBJECTIVE
Expression of tumor suppressor gene, MASPIN, is associated with inhibition of tumor cell invasion and metastasis. Loss of or decreased expression of Maspin is found frequently in breast and prostate cancer cells. The objective of this study is to investigate Maspin expression in prostate tumor specimens and explore the mechanisms of hormonal regulation of Maspin expression in prostate tumors.


METHODS
Immunohistochemical staining of Maspin expression was performed on surgical whole-mounted prostate specimens. The expression of Maspin was scored on individual tumors. Correlation of Maspin expression with clinicopathological features was analyzed for statistical significance. Androgen ablation-induced Maspin expression was analyzed by Maspin promoter luciferase reporter assay and quantitative reverse transcription-PCR analysis of endogenous Maspin expression in LNCaP cells in vitro and in animal model.


RESULTS
Comprehensive evaluation of Maspin expression profile in multiple tumor foci from whole mounted prostate specimens of prostate cancer patients revealed absence of Maspin expression in a significant fraction (63%). However, Maspin expression is significantly higher in tumor specimens (92%) of patients treated with neoadjuvant androgen ablation therapy before radical prostatectomy. LNCaP cells cultured in androgen-depleted medium show induction of Maspin promoter activity in a promoter luciferase reporter assay. In addition, Maspin expression is increased after castration in LNCaP prostate cancer cells derived tumors in nude mice.


CONCLUSIONS
Maspin expression is frequently absent in primary prostate cancers. Up-regulation of MASPIN in response to androgen ablation strongly suggests a physiological role of Maspin in growth inhibition and/or apoptosis of prostate cancer cells during androgen ablation.
Zou
Zhiqiang
Z
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, Maryland 20852, USA.
Zhang
Wei
W
Young
Denise
D
Gleave
Martin G
MG
Rennie
Paul
P
Connell
Theresa
T
Connelly
Roger
R
Moul
Judd
J
Srivastava
Shiv
S
Sesterhenn
Isabell
I
D000368:Aged; D000728:Androgens / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D011506:Proteins; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; C085344:SERPIN-B5; D015843:Serpins; D008156:Luciferases