PRESENCE OF THE 2 GROWTH-HORMONE RECEPTOR MESSENGER-RNA ISOFORMS IN HUMAN BREAST-CANCER

In the present study, we have investigated specific growth hormone (CH) receptor gene expression in breast cancer cell lines and tissues. By Northern blot analysis, using a human GH receptor cDNA probe, the classically observed 4.7-kilobase GH receptor mRNA was evidenced in 2 of 29 cancer biopsies and in the MCF7 and T47-D cell lines. Reverse transcription coupled to PCR was used to amplify the GH receptor sequence encompassing a part of the extracellular domain as well as the transmembrane domain. An amplification product of the expected size (456 base pairs) was observed in 28 of 29 breast biopsies and in all the breast cancer cell lines studied (T47-D, MCF7, MDA-MB-231, and BT-20). The reverse transcription-PCR product was shown to be specific by Southern blot hybridization with the GH receptor cDNA probe and by specific cleavage of the amplified products with restriction enzymes. For the first time, the expression of GH receptor gene in breast cancer cell lines and biopsies is demonstrated in this study, suggesting a GH-specific action in tumor development. Additionally, the two isoforms of the human GH receptor (hGHR) mRNA, one containing exon 3 (hGHR-wt mRNA) and one excluding exon 3 (hGHR-d3 mRNA), were found to be expressed independently or simultaneously (29 tumors analyzed). The presence of hGHR-d3 mRNA appears to be patient specific, as demonstrated by comparing the expression pattern of both mRNAs between tumor biopsy and lymphocytes of the same patient.