Novel alternatively spliced isoform of synuclein gamma

Introduction: Since Synuclein γ (SNCG) is found highly expressed in advanced breast cancer it was initially described as breast-cancer specific gene (BCSG1). Clinical studies demonstrate the correlation of high SNCG expression with advanced stages, metastasis and poor prognosis in breast and ovarian carcinomas, i.e. reduced relapse-free and overall survival periods. In vitro analyses revealed a SNCG-dependent stimulation of ligand-dependent transcriptional activity of ERα. So far, four mRNA isoforms of SNCG were described, but only isoforms-1 and -2 code for active proteins. For the first time, we analyzed expression levels of SNCG mRNA isoforms in regard to hypoxia or acidosis, in vitro in endometrial cancer cells.

Methods: In vitro tests under hypoxic, acidic or control conditions with consecutive RNA and protein analysis.

Results: In comparison to the reference breast cancer cell line, endometrial cancer cell lines displayed a general significantly reduced expression of SNCG isoform-1, -2, -3 and -4. In contrast, a novel, shortened mRNA variant of isoform-2 was identified in endometrial cancer cells. Hypoxia and acidosis triggered a marked up-regulation of the novel isoform-2-short, while the expression of constitutive isoform-2 did not significantly change under altered conditions. Immunohistochemistry and Western blot revealed a hypoxia- and acidosis- dependent increase in SNCG protein expression.

Conclusion: We hypothesize, that the novel SNCG isoform-2-short bears a specific oncogenic potential in endometrial cancer, since it occurred in elevated levels under typical epiphenomena of solid tumors in vitro. Furthermore we postulate that this novel isoform is capable to code for a biologically active protein isoform.