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. Copyright 2000 S. Karger AG, Basel