Functional Characterization of a Novel Pro-Apoptotic Transcription Regulatory Protein in Ovarian Cancer

摘要

In an effort to identify genetic changes involved in ovarian cancer (OvCa) development, we performed differential display-PCR, cDNA microarray and suppression subtraction hybridization analyses (SHH) to identify early genetic alterations associated with OvCa. These studies resulted in identification of several genes differentially expressed in OvCa, including a novel gene encoding a transcription elongation-like protein with the ability to induce apoptosis and suppress cancer cell growth. We named the protein ProApoptotic Protein on chromosome X (PAPX). Pro-apoptotic protein on X (PAPX) is a novel nuclear protein with sequence homology to transcription elongation factor like 1 (TCEAL1); (1) PAPX expression is down-regulated in majority of ovarian cancer cell lines and primary tumors; (2) Re-expression of PAPX induces cell death and attenuates cell growth. We therefore proposed to study the functional role of PAPX as a candidate tumor suppressor in ovarian cancer. We proposed to (1) determine effect of PAPX on tumor and cell growth in vivo and in vitro; (2) analyze genes regulated by PAPX by transcriptional profiling using microarray chips; and (3) identify proteins that interact with PAPX and elucidate the function of PAPX related to tumor suppression.