Identification of mu-crystallin as an androgen-regulated gene in human prostate cancer.
BACKGROUND
Androgen receptor (AR) signaling is implicated in prostate cancer progression. Therefore, identification of AR downstream genes is potentially important for selection of novel markers and therapy targets in prostate cancer.


METHODS
Expression of a thyroid hormone T3-binding protein mu-crystallin (CRYM) mRNA and protein in cell lines was evaluated by real-time PCR and Western blot, respectively. CRYM expression in vivo was analyzed in patients' samples by immunohistochemistry. The effects of androgen and T3 on proliferation of MDA PCa 2b cells were assessed by (3)H-thymidine uptake assay.


RESULTS
CRYM expression was detected in AR-positive LNCaP and MDA PCa 2b cells. In MDA PCA 2b cells, CRYM was regulated by androgens. Androgen-induced CRYM expression was diminished by antiandrogens or AR siRNA. Inhibition of transcription by alpha-amanitin caused a reduction in CRYM mRNA. The lack of CRYM expression was noted in LAPC-4 cells and in AR-negative prostate cancer cell lines PC-3 and DU-145. CRYM protein was increased in cancer tissue and decreased in samples from patients after hormonal therapy. In samples from patients with therapy-refractory cancer CRYM was not detectable. We also found that androgens and T3 have additive effects on stimulation of MDA PCa 2b cells proliferation.


CONCLUSIONS
CRYM is a novel androgen-regulated gene whose expression is elevated in prostate cancer but down-regulated in castration therapy-resistant tumors.
Department of Urology and Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Kamilla
K
Malinowska
Ilaria T
IT
Cavarretta
Martin
M
Susani
Oliver A
OA
Wrulich
Florian
F
Uberall
Lukas
L
Kenner
Zoran
Z
Culig
D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D003459:Crystallins / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D013963:Thyroid Hormones / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000090803:mu-Crystallins; D000097810:Thyroid Hormone-Binding Proteins
D059002:Androgen Receptor Antagonists; D000728:Androgens; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003459:Crystallins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013963:Thyroid Hormones; D000090803:mu-Crystallins; D000097810:Thyroid Hormone-Binding Proteins; C000716469:CRYM protein, human