p53 mutation status is a primary determinant of placenta-specific protein 1 expression in serous ovarian cancers.
Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppressor p53 was shown in vitro to inhibit PLAC1 transcription by compromising the P1, or distal/cancer, promoter. We sought to determine if this phenomenon occurs in primary patient tumors as well. Furthermore, we wanted to know if p53 mutation influenced PLAC1 expression as compared with wild-type. We chose to study serous ovarian tumors as they are well known to have a high rate of p53 mutation. We report herein that the phenomenon of PLAC1 transcription repression does occur in serous ovarian carcinomas but only when TP53 is wild-type. We find that mutant or absent p53 protein de-represses PLAC1 transcription. We further propose that the inability of mutant p53 to repress PLAC1 transcription is due to the fact that the altered TP53 protein is unable to occupy a putative p53 binding site in the PLAC1 P1 promoter thus allowing transcription to occur. Finally, we show that PLAC1 transcript number is significantly negatively correlated with patient survival in our samples. Thus, we suggest that characterizing tumors for TP53 mutation status, p53 protein status and PLAC1 transcription could be used to predict likely prognosis and inform treatment options in patients diagnosed with serous ovarian cancer.
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Eric J
EJ
Devor
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Jesus
J
Gonzalez-Bosquet
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Akshaya
A
Warrier
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Henry D
HD
Reyes
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Nonye V
NV
Ibik
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Brandon M
BM
Schickling
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Andreea
A
Newtson
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Michael J
MJ
Goodheart
Department of Obstetrics and Gynecology, University of Iowa Carver College of Medicine and The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Kimberly K
KK
Leslie
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C415583:PLAC1 protein, human; D011257:Pregnancy Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53