Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer.
Transgelin is an actin-binding protein shown to be tumour-suppressive. Loss of transgelin expression in transformed cells is associated with oncogenesis. This study aimed to determine whether transgelin expression was suppressed in prostate cancer. An in silico meta-analysis with public-domain expressed-sequence-tag libraries of normal human prostate epithelium, prostatic intraepithelial neoplasia, invasive carcinoma and metastasised lesions predicted decreased transgelin expression with disease progression. Similarly, analysis of Affymetrix gene chip data and the Oncomine database indicated that transgelin was one the 2% most significant of all down-regulated genes in response to prostate cancer. Analysis by quantitative reverse transcription with the polymerase chain reaction (qRT-PCR) of patient biopsies determined transgelin expression to be significantly lower in prostate tumour tissue than in matched normal tissue. Similarly, qRT-PCR and Western blot analysis of representative prostate cancer cell lines demonstrated significantly lower levels of transgelin mRNA and protein in all but the DU145 prostate cancer cell line. Increased expression of TAGLN and increased transgelin protein in response to treatment with transforming growth factor-beta suggested that reduced expression in prostate cancer was not attributable to gene promoter suppression by hypermethylation. Gene ontology function analysis highlighted the importance of transgelin in the co-deregulation of actin-binding proteins. Thus, transgelin is suppressed during prostate cancer progression and seems to be an important factor in the dysregulation of the actin cytoskeleton.
Prasad
Priya D
PD
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
Stanton
Jo-Anne L
JA
Assinder
Stephen J
SJ
D000199:Actins / Q000378:metabolism; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D018450:Disease Progression; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000199:Actins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D016212:Transforming Growth Factor beta; C051615:transgelin