17-BETA-HYDROXYSTEROID DEHYDROGENASE-1 PSEUDOGENE IS DIFFERENTIALLY TRANSCRIBED - STILL A CANDIDATE FOR THE BREAST-OVARIAN CANCER SUSCEPTIBILITY GENE (BRCA1)

BRCA1, the susceptibility gene for hereditary breast-ovarian cancer, i s located on chromosome 17q12-21 but has not yet been identified. Two tandem oestradiol 17 beta hydroxysteroid dehydrogenase genes (17HSD) a re assigned to this region. The active 17HSDII gene encodes the normal enzyme which regulates local synthesis of oestrogens, whereas 17HSDI is considered to be a pseudogene. We used reverse transcription couple d to polymerase chain reaction (RT-PCR) and found that the 17HSD gene was also transcribed in half of the human cell lines and most of the b iopsies studied, suggesting that 17HSDI could modulate normal 17HSDII activity in oestrogen target cells. We hypothesize that altered 17HSDI gene expression could lead to both hereditary and/or sporadic breast cancer by increasing local oestrogen concentration and that it is stil l a potential candidate for BRCA1. (C) 1994 Academic Press, Inc.