K. Laud et al., Characterization and modulation of a prolactin receptor mRNA isoform in normal and tumoral human breast tissues, INT J CANC, 85(6), 2000, pp. 771-776
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.