Identification of exon-deleted progesterone receptor mRNAs in human uterine endometrial cancers.
We demonstrated the expression of various exon-deleted progesterone receptor (PR) variant mRNAs in human uterine endometrial cancers using the reverse transcription-polymerase chain reaction-DNA sequencing analyses. In addition to PR wild-type mRNA, exon 4-deleted, exon 6-deleted, exon 3,4-deleted, exon 5,6-deleted, exon 4,5,6-deleted and exon 3,4,5,6-deleted PR variant mRNAs were identified. The exon 6-deleted and exon 5,6-deleted PR variant mRNAs lacked encoding for the steroid-binding domain. The exon 4-deleted, exon 3,4-deleted, exon 4,5,6-deleted and exon 3,4,5,6-deleted PR variant mRNAs lacked encoding for the DNA-binding domain in addition to encoding for the steroid-binding domain. While the exon 4-deleted, exon 6-deleted and exon 3,4-deleted PR variant mRNAs were observed in all samples analyzed, the exon 5,6-deleted, exon 4,5,6-deleted and/or exon 3,4,5,6-deleted PR variant mRNAs could not be detected in some cases, especially in poorly differentiated adenocarcinoma as compared with well-differentiated and moderately differentiated adenocarcinomas. The present study demonstrates the coexpression of PR exon-deleted variant mRNAs with the wild-type in uterine endometrial cancers. All translated variant proteins might possess functional diversity and might modify the progestational action of wild-type PR, and the expression of some PR variant mRNAs may be lost as endometrial cancer cells undergo dedifferentiation.
Misao
R
R
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu, Japan. misao@cc.gifu-u.ac.jp
Nakanishi
Y
Y
Sun
W
W
Iwagaki
S
S
Fujimoto
J
J
Tamaya
T
T
D016889:Endometrial Neoplasms / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008875:Middle Aged; D012313:RNA; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
C034477:RNA primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011980:Receptors, Progesterone; D012313:RNA