Expression of the actin-associated protein transgelin (SM22) is decreased in prostate cancer

Abstract

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.

Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer

“…5C and D; refs. [36][37][38][39][40][41][42]. These observations therefore provide a mechanism for decreased motility, which corresponds well to the observed phenotype and the expected role of the Mediator complex.…”

“…To systematically investigate the mechanism of action, senexin A-treated DU-145 cells were subjected to RNA sequencing. Among the genes most strongly upregulated, several have previously been implicated in reduced migration of cancer cells or as being repressed during prostate cancer progression such as such as TAGLN (36,37), CDH1 (38, 39), CDH3 (40), TPM1 (41), or MYL-9 (refs. 39, 42; Fig.…”

MicroRNA let-7c Suppresses Androgen Receptor Expression and Activity via Regulation of Myc Expression in Prostate Cancer Cells

“…The second dataset (GDS2547) (24) compared normal prostate specimens without any pathology, normal prostate adjacent to tumor, primary prostate tumor, and metastatic prostate cancer. Relative levels of expression of Lin28, AR, and Myc were determined by comparison of single channel counts and expressed as a percentage of the highest count in the data set (25). Significant differences between groups were determined by Microsoft Excel Tools.…”

Comparative Proteomic Study of Proteins in Prostate Cancer and Benign Hyperplasia Cells

“…It is known, that transgelins are actin-associated proteins that participate in cytoskeleton formation [42]. Accordingly, the expression changes of transgelin genes (TAGLN, TAGLN2) during cancerogenesis can have an influence on cell motility, and also on invasiveness and Table 1).…”

“…However the data concerning the character of expression changes of transgelin genes at prostate cancer are conflicting. So, Prasad et al [42] have recently reported that transgelin level is decreased in various types of prostate cancer cultured cells (except Du-145), and Lee et al [43] have the opposite observations that level of transgelin is essentially increased in malignant prostate cells.…”