Devor Eric J, Reyes Henry D, Gonzalez-Bosquet Jesus, Warrier Akshaya, Kenzie Susan A, Ibik Nonye V, Miller Marina D, Schickling Brandon M, Goodheart Michael J, Thiel Kristina W, Leslie Kimberly K
*Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine; †Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City; ‡Des Moines University, College of Osteopathic Medicine, Des Moines; §Department of Biology, Lincoln University, Pennsylvania; and ∥Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.
Int J Gynecol Cancer. 2017 May;27(4):784-790. doi: 10.1097/IGC.0000000000000957.
Expression of the trophoblast-specific gene placenta-specific protein 1 (PLAC1) has been detected in a wide variety of cancers. However, to date, PLAC1 expression has not been shown in cervical cancer. We have carried out a preliminary study that shows for the first time that PLAC1 is expressed in cervical cancers.
A total of 16 primary cervical tumors were obtained from patients shown to be human papillomavirus (HPV) 16/18 positive. Total cellular RNA, genomic DNA, and total protein were purified from each tumor. These materials were then used to determine PLAC1 expression, TP53 mutation status, and p53 expression.
The PLAC1 expression was demonstrated in all 16 primary cervical tumors. The highest levels of expression were found in the more aggressive squamous and adenosquamous histologic types compared with adenocarcinomas. Moreover, the proportion of total PLAC1 message coming from the P1 promoter, also termed the distal or cancer promoter, was significantly greater in the more aggressive squamous and adenosquamous histologic types compared with adenocarcinomas. Finally, in spite of all 16 tumors being HPV-16/18 positive, 3 of 8 squamous cell cancers and 2 of 5 adenocarcinomas expressed wild-type p53 protein. Consistent with the recently shown suppression of the PLAC1P1 promoter by wild-type p53, these p53 positive tumors displayed among the lowest P1-specific PLAC1 expression levels.
The PLAC1 expression has been demonstrated for the first time in cervical cancers. This preliminary study has further revealed a complex relationship between PLAC1 expression, cervical cancer histologic type, p53, and HPV type that requires further investigation.
滋养层特异性基因胎盘特异性蛋白1(PLAC1)已在多种癌症中被检测到表达。然而,迄今为止,尚未在宫颈癌中发现PLAC1的表达。我们进行了一项初步研究,首次表明PLAC1在宫颈癌中表达。
从人乳头瘤病毒(HPV)16/18阳性患者中获取了16个原发性宫颈肿瘤。从每个肿瘤中纯化总细胞RNA、基因组DNA和总蛋白。然后使用这些材料来确定PLAC1的表达、TP53突变状态和p53表达。
在所有16个原发性宫颈肿瘤中均证实了PLAC1的表达。与腺癌相比,在侵袭性更强的鳞状和腺鳞癌组织学类型中发现了最高水平的表达。此外,与腺癌相比,来自P1启动子(也称为远端或癌症启动子)的总PLAC1信使比例在侵袭性更强的鳞状和腺鳞癌组织学类型中显著更高。最后,尽管所有16个肿瘤均为HPV - 16/18阳性,但8例鳞状细胞癌中的3例和5例腺癌中的2例表达野生型p53蛋白。与最近显示的野生型p53对PLAC1P1启动子的抑制作用一致,这些p53阳性肿瘤显示出最低的P1特异性PLAC1表达水平。
首次在宫颈癌中证实了PLAC1的表达。这项初步研究进一步揭示了PLAC1表达、宫颈癌组织学类型、p53和HPV类型之间的复杂关系,需要进一步研究。