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Characterization and modulation of a prolactin receptor mRNA isoform in normal and tumoral human breast tissues
Author(s) -
Laud Karine,
Gourdou Isabelle,
Belair Lucette,
Peyrat JeanPhilippe,
Djiane Jean
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000315)85:6<771::aid-ijc5>3.0.co;2-y
Subject(s) - alternative splicing , gene isoform , mammary gland , biology , exon , frameshift mutation , prolactin , endocrinology , rna splicing , messenger rna , extracellular , northern blot , receptor , medicine , carcinogenesis , ductal carcinoma , microbiology and biotechnology , gene , breast cancer , cancer , hormone , genetics , rna
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. Int. J. Cancer 85:771–776, 2000. © 2000 Wiley‐Liss, Inc.