EXPRESSION OF HUMAN PROSTATE-SPECIFIC GLANDULAR KALLIKREIN PROTEIN (HK2) IN THE BREAST-CANCER CELL-LINE T47-D

Human glandular kallikrein (hK2) protein, like prostate-specific antig en (PSA), is produced mainly in prostatic epithelium. It may be useful as a new diagnostic indicator for prostate cancer. Recently, a number of hK2-specific monoclonal antibodies have been developed that enable us to detect hK2 protein in human prostate tissue, seminal fluid, and sera. Whether hK2 can he expressed, like PSA, in nonprostatic cells i s not known. In this study, we have characterized the presence of hK2 in an androgen-responsive breast cancer cell line T47-D at both the pr otein and mRNA levels with an immunoassay, Western blot analysis, Nort hern blot analysis, and the reverse transcription-PCR. Using a sensiti ve immunoassay with monoclonal antibodies to hK2, we found that T47-D cells could be induced with androgens, mineralocorticoids, glucocortic oids, and progestins to produce significantly more hK2 than PSA. Estro gens failed to mimic the effect of the other steroids, blocking instea d the stimulatory effect of androgens. Androgen induction of hK2 in T4 7-D cells was dose dependent. More interestingly, we found that the hK 2 in androgen-induced T47-D cell spent media appears to be the pro-for m of hK2 rather than mature hK2. Our study demonstrates that hK2, a se rine protease thought to be found only in prostate-related tissues and fluids, is also produced in a breast cancer cell line T47-D after ste roid stimulation. This finding suggests that hK2 may have a potential role in breast cancer as well as prostatic cancer and will be the impe tus for further studies of hK2 distribution and function.