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A novel splice variant of the β‐tropomyosin ( TPM2 ) gene in prostate cancer
Author(s) -
Assinder Stephen J.,
Au Edith,
Dong Qihan,
Winnick Clare
Publication year - 2010
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20626
Subject(s) - biology , lncap , prostate cancer , tropomyosin , gene isoform , exon , actin , prostate , splice , microbiology and biotechnology , cancer , cancer research , gene , genetics
Abstract Decreased expression of high molecular weight isoforms of tropomyosin (Tm) is associated with oncogenic transformation and is evident in cancers, with isoform Tm1 seemingly an important tumor suppressor. Tm1 expression in prostate cancer has not previously been described. In this study, while demonstrating suppressed levels of Tm1 in the prostate cancer cell lines LNCaP, PC3, and DU‐145 compared to normal prostate epithelial cell primary isolates (PrEC), a novel splice variant of the TPM2 gene was identified. Quantitative RT‐PCR determined significantly greater levels of the transcript variant in all three prostate cancer cell lines than in normal prostate epithelial cells. Characterization of this novel variant demonstrated it to include exon 6b, previously thought unique to the muscle‐specific β‐Tm isoform, with an exon arrangement of 1–2–3–4–5–6a–6b–7–8–10. Inclusion of exon 6b introduces a premature stop codon directly following the 6a–6b exon boundary. Western blot analysis demonstrated the presence of a truncated protein in prostate cancer cell lines that was absent in normal prostate epithelial cells. It is hypothesized that this truncated protein will result in suppression of Tm1 polymer formation required for actin filament association. The lack of Tm polymer–actin association will result in loss of the stable actin microfilament organization and stress fiber formation, a state associated with cell transformation. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.