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 breast 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 lobular) 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 alternative exon 6 splicing. This isoform has a 170 bp deletion in its extracellular sub-domain that induces a frameshift. Thus, the predicted amino-acid sequence should encode a putative soluble protein with the N-terminal sub-domain of the hPRL-R and 10 additional carboxy-terminal residues. This isoform should not bind PRL as previously demonstrated by other experiments. Moreover, the ratio of full-length to deleted form of hPRL-R transcripts differs 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 mechanism 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 gland.
Laud
K
K
Unité d'Endocrinologie Moléculaire, Institut National de la Recherche Agronomique, Jouy-en -Josas, France. klaud@biotec.jouy.inra.fr
Gourdou
I
I
Belair
L
L
Peyrat
J P
JP
Djiane
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D012333:RNA, Messenger; D011981:Receptors, Prolactin