Characterization and modulation of a prolactin receptor mRNA isoform in normal and tumoral human breast tissues

The role of prolactin (PRL) and its specific receptor (R-PRL) in human brea st tumorigenesis remains unclear. We have investigated here the presence of extracellular-deleted hPRL-R isoforms in normal human breast, fibrocystic disease, primary breast carcinoma (ductal carcinoma, ductulo-lobular and lo bular) and breast cancer cell lines (T47-D and MCF-7). RT-PCR and Southern blot analysis demonstrated the expression of full-length hPRL-R transcript in all samples tested. We also detected a hPRL-R transcript generated by al ternative exon 6 splicing. This isoform has a 170 bp deletion in its extrac ellular sub-domain that induces a frameshift. Thus, the predicted amino-aci d sequence should encode a putative soluble protein with the N-terminal sub -domain of the hPRL-R and 10 additional carboxy-terminal residues. This iso form should not bind PRL as previously demonstrated by other experiments. M oreover, the ratio of full-length to deleted form of hPRL-R transcripts dif fers from normal to tumoral breast tissue. This ratio is higher in tumoral mammary gland than in normal tissue. Our data suggest that the alternative splicing of the hPRL-R gene towards the deleted transcript may be a mechani sm to down- or up-regulate the expression of the native transcript of hPRL- R in accordance to the physiological or pathological state of the mammary g land. (C) 2000 Wiley-Liss, Inc.