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, is located on chromosome 17q12-21 but has not yet been identified. Two tandem oestradiol 17 beta hydroxysteroid dehydrogenase genes (17HSD) are 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 coupled to polymerase chain reaction (RT-PCR) and found that the 17HSDI gene was also transcribed in half of the human cell lines and most of the biopsies 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 still a potential candidate for BRCA1.