Differential expression of TGFbeta-stimulated clone 22 in normal prostate and prostate cancer.
The transforming growth factor-beta (TGFbeta) superfamily and its downstream effector genes are key regulators of epithelial homeostasis. Altered expression of these genes may be associated with malignant transformation of the prostate gland. The cDNA array analysis of differential expression of the TGFbeta superfamily and functionally related genes between patient-matched noncancerous prostate (NP) and prostate cancer (PC) bulk tissue specimens highlighted two genes, namely TGFbeta-stimulated clone-22 (TSC-22) and Id4. Verification of their mRNA expression by real-time PCR in patient-matched NP and PC bulk tissue, in laser-captured pure epithelial and cancer cells and in NP and PC cell lines confirmed TSC-22 underexpression, but not Id4 overexpression, in PC and in human PC cell lines. Immunohistochemical analysis showed that TSC-22 protein expression in NP is restricted to the basal cells and colocalizes with the basal cell marker cytokeratin 5. In contrast, all matched PC samples lack TSC-22 immunoreactivity. Likewise, PC cell lines do not show detectable TSC-22 protein expression as shown by immunoblotting. TSC-22 should be considered as a novel basal cell marker, potentially useful for studying lineage determination within the epithelial compartment of the prostate. Conversely, lack of TSC-22 seems to be a hallmark of malignant transformation of the prostate epithelium. Accordingly, TSC-22 immunohistochemistry may prove to be a diagnostic tool for discriminating benign lesions from malignant ones of the prostate. The suggested tumour suppressor function of TSC-22 warrants further investigation on its role in prostate carcinogenesis and on the TSC-22 pathway as a candidate therapeutic target in PC.
Rentsch
Cyrill A
CA
Urology Research Laboratory, Departments of Urology and Clinical Research, University of Bern, Switzerland.
Cecchini
Marco G
MG
Schwaninger
Ruth
R
Germann
Markus
M
Markwalder
Regula
R
Heller
Manfred
M
van der Pluijm
Gabri
G
Thalmann
George N
GN
Wetterwald
Antoinette
A
D000368:Aged; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C099726:TSC22D1 protein, human; D016212:Transforming Growth Factor beta