Cathepsin D, a lysosomal protease, is induced by estrogens in hormone responsive breast cancer cells, by progesterone in normal endometrium and expressed at high constitutive levels in estrogen receptor (ER)-negative cells. To investigate whether ER is the only transacting factor missing in ER negative cells to obtain estrogen regulation, we transfected an ER cDNA expression vector (HEO) into ER-negative Hela cells and showed that it could recover estrogen sensitivity for cathepsin D gene expression but not for cell growth regulation. These results show i. that the expression of an endogenous gene in humans can be stimulated by estradiol after ER supplementation, indicating that Hela cells contain sufficient amounts of the other transcription factors required for cathepsin D estrogen inducibility; ii. that cathepsin D expression is stimulated by estrogens in this cervix cancer cell line, as it is in the ER-positive breast cancer cells, which contrasts with its regulation by progesterone in normal endometrial cells.