Analysis of the human CGB/LHB gene cluster in breast tumors by real-time quantitative RT-PCR assays

The six genes of the human chorionic gonadotropin beta subunit (CGB) and th e gene of the luteinizing hormone beta subunit (LHB) are located in a clust er that spans 50 kb on chromosome 19q13.3. Only genes CGB7, B8, B5 and B3 c an generate the human chorionic gonadotropin (hCG) beta molecule. The other two genes, CGB1 and B2, encode unidentified proteins. We have previously s hown that malignant breast transformation is associated with the emergence of the 'trophoblastic' CGB genes (B8, B5 and B3), in addition to the CGB7 g ene, which is the only CGB gene expressed in normal breast tissue. To bette r understand the dysregulation of the CGB/LHB gene cluster in breast cancer , we have developed real-time quantitative RT-PCR assays to analyze each su bgroup of genes (the overall CGB genes, CGB1 and B2 together, and LHB alone ) in 17 unilateral invasive primary breast tumor RNAs. We also analyzed the chorionic gonadotropin cw (CGA) gene coding for the human CGA subunit. We found that the emergence of the 'trophoblastic' CGB genes in breast tumors is (i) accompanied by an increase in the total CGB mRNA steady-state level, (ii) mainly due to overexpression of genes CGB8, B5 and B3 (expression of other genes in the CGB/LHB gene cluster (CGB7, B2, B1 and LHB) changes litt le if at all), and (iii) not accompanied by overexpression of the CGA gene which is necessary to produce ectopic hCG heterodimeric hormone in breast t umor cells, these latter which yet expressed the LH/CG receptor. These obse rvations suggest that it is mainly the CGB8, B5 and B3 genes which are upre gulated in the 19q13.3 CGB gene cluster in breast tumors. They also point t o a role (like growth factor) of the CGP subunit in breast tumorigenesis, v ia a novel pathway independent of the LH/CG receptor. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.