The significance of LMO2 expression in the progression of prostate cancer

• Published in: The Journal of pathology Vol. 211; no. 3; pp. 278 - 285
• Main Authors: Ma, S, Guan, XY, Beh, PSL, Wong, KY, Chan, YP, Yuen, HF, Vielkind, J, Chan, KW
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2007; Wiley
• Subjects: Adaptor Proteins, Signal Transducing; Adenocarcinoma - pathology; Aged; Aged, 80 and over; Biological and medical sciences; Blotting, Western - methods; Cell Line, Tumor; Chi-Square Distribution; DNA-Binding Proteins - genetics; E-cadherin; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); LIM Domain Proteins; LMO2; Male; Medical sciences; Metalloproteins - genetics; metastasis; Middle Aged; Neoplasm Staging; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; prostate cancer; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumors of the urinary system; Urinary tract. Prostate gland; Anatomic pathology; Urinary system disease; Prostate disease; Tumor progression; Cell adhesion molecule; LMO2; Malignant tumor; Metastasis; Male genital diseases; E Cadherin; Prostate cancer; E-cadherin
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2109

LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high‐grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real‐time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen‐dependent (AD) and androgen‐independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down‐regulation of E‐cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E‐cadherin expression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.