Lee Yong Hoi, Pang Siew Wai, Tan Kuan Onn
Cancer Biology Group, Department of Biological Sciences, Faculty of Science and Technology, Sunway University, No.5 Jalan Universiti, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.
Cancer Biology Group, Department of Biological Sciences, Faculty of Science and Technology, Sunway University, No.5 Jalan Universiti, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.
Biochem Biophys Res Commun. 2016 Apr 22;473(1):224-229. doi: 10.1016/j.bbrc.2016.03.083. Epub 2016 Mar 19.
PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction.
副肿瘤性 Ma 家族（PNMA）成员之一的 PNMA2，是通过使用副肿瘤性疾病患者的抗血清进行表达克隆鉴定出来的。组织表达研究表明，PNMA2 在正常人类大脑中主要表达；然而，该蛋白在从副肿瘤患者获得的许多肿瘤组织中被发现有异常表达谱。PNMA2 的异常表达谱表明它可能在肿瘤发生中起重要作用；然而，除了蛋白质表达和免疫学研究外，PNMA2 的生理作用仍不清楚。为了确定 PNMA2 在肿瘤发生中的潜在作用及其与 PNMA 家族成员 MOAP-1（PNMA4）和 PNMA1 的功能关系，构建了编码各自蛋白质的表达构建体用于体外和体内研究。我们的研究表明，过表达的 MOAP-1 和 PNMA1 在 MCF-7 细胞中促进了凋亡和化学敏感性，细胞核浓缩和 Annexin-V 阳性的 MCF-7 细胞证明了这一点；然而，当与 PNMA2 在 MCF-7 细胞中共表达时，这些蛋白介导的作用被显著抑制或消除。此外，免疫共沉淀研究表明，PNMA1 和 MOAP-1 彼此不结合，但很容易与 PNMA2 形成各自的异二聚体，这表明 PNMA2 通过异二聚体相互作用作为 MOAP-1 和 PNMA1 的拮抗剂发挥作用。
