title: Elevated expression of the serine-arginine protein kinase 1 gene in ovarian cancer and its role in Cisplatin cytotoxicity in vitro.
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.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.forename: Christopher
authors.initials: C
authors.lastname: Andrews
authors.forename: Amy
authors.initials: A
authors.lastname: Beck
authors.forename: Olajumoke
authors.initials: O
authors.lastname: Amuwo
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Black
authors.forename: Ruea-Yea
authors.initials: RY
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D034741:RNA, Small Interfering; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin