Abstract
Alternatively spliced variants of several oncogenes and tumor suppressors have been shown to be important for their tumorigenicity. In the present study we have tested whether serine-arginine protein kinase 1 (SRPK1), a major regulator of splicing factors, is involved in ovarian cancer progression and plays a role in chemo-sensitivity. By Western blot analyses, SRPK1 protein was found to be overexpressed in 4 out of 6 ovarian cancer cell lines as compared with an immortalized ovarian surface epithelial cell line; and in 55% of ovarian tumor samples as compared with non-neoplastic ovarian tissue samples. Reduction of SRPK1 expression using small interfering RNA (siRNA) encoding small hairpin RNA in ovarian cancer cells led to (i) reduced cell proliferation rate, slower cell cycle progression and compromised anchorage-independent growth and migration ability in vitro, (ii) decreased level of phosphorylation of multiple serine-arginine proteins, and P44/42MAPK and AKT proteins, and (iii) enhanced sensitivity to cisplatin. Together, these results suggest that elevated SRPK1 expression may play a role in ovarian tumorigenesis and SRPK1 may be a potential target for ovarian cancer therapy.
Highlights
It has been estimated that 35–59% of human genes are alternatively spliced, which contributes greatly to the complexity of human cellular functions [1,2]
We have previously found that inactivation of the yeast SR protein kinase Sky1p confers resistance to cisplatin [22]
Since gene levels in long term cultured cell lines may be altered, we examined serine-arginine protein kinase 1 (SRPK1) expression in archived ovarian cancer (OVCa) tumor samples from OVCa patients who were treated with platinum-regimens after surgery
Summary
It has been estimated that 35–59% of human genes are alternatively spliced, which contributes greatly to the complexity of human cellular functions [1,2]. While phosphorylated SR proteins are required for initiating spliceosome assembly at the earliest stage, dephosphorylation is essential for splicing to take place in the spliceosome [13,14]. Overexpression of SRPK1 protein has been documented in acute type Adult T-cell leukemia [16], chronic myelogenous leukemia [17] pancreatic, breast, and colon cancers [18,19,20]. SRPK1 is expressed in adult male germ cells, but generally not in most other normal adult tissues, suggesting a cancer/testis-like distribution [16,21]. Together, these studies suggest that SRPK1 is likely to play an important role in cancer development
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