Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Genes Cells. 2022 Nov;27(11):633-642. doi: 10.1111/gtc.12980. Epub 2022 Aug 25.
Ovarian cancer (OC) is the fifth most common cancer of female cancer death and leading cause of lethal gynecological cancers. High-grade serous ovarian carcinoma (HGSOC) is an aggressive malignancy that is rapidly fatal. Many cases of OC show amplification of the 8q24 chromosomal region, which contains the well-known oncogene MYC. Although MYC amplification is more frequently observed in OCs than in other tumor types, due to the large size of the 8q24 amplicon, the functions of the vast majority of the genes it contains are still unknown. The TIGD5 gene is located at 8q24.3 and encodes a nuclear protein with a DNA-binding motif, but its precise role is obscure. We show here that TIGD5 often co-amplifies with MYC in OCs, and that OC patients with high TIGD5 mRNA expression have a poor prognosis. However, we also found that TIGD5 overexpression in ovarian cancer cell lines unexpectedly suppressed their growth, adhesion, and invasion in vitro, and also reduced tumor growth in xenografted nude mice in vivo. Thus, our work suggests that TIGD5 may in fact operate as a tumor suppressor in OCs rather than as an oncogene.
卵巢癌(OC)是女性癌症死亡的第五大常见癌症,也是导致致命妇科癌症的主要原因。高级别浆液性卵巢癌(HGSOC)是一种侵袭性恶性肿瘤,死亡率极高。许多 OC 病例显示 8q24 染色体区域的扩增,该区域包含着著名的癌基因 MYC。尽管 MYC 扩增在 OC 中比在其他肿瘤类型中更为常见,但由于 8q24 扩增子的巨大尺寸,其包含的绝大多数基因的功能仍然未知。TIGD5 基因位于 8q24.3,编码具有 DNA 结合基序的核蛋白,但它的确切作用尚不清楚。我们在这里表明,TIGD5 经常与 MYC 在 OC 中共同扩增,并且 OC 患者中 TIGD5 mRNA 表达水平高的患者预后不良。然而,我们还发现,在卵巢癌细胞系中过表达 TIGD5 出人意料地抑制了它们的体外生长、黏附和侵袭,并且还减少了体内异种移植裸鼠的肿瘤生长。因此,我们的工作表明,TIGD5 实际上可能在 OC 中作为肿瘤抑制因子发挥作用,而不是癌基因。