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 the gene of the luteinizing hormone beta subunit (LHB) are located in a cluster that spans 50 kb on chromosome 19q13.3. Only genes CGB7, B8, B5 and B3 can generate the human chorionic gonadotropin (hCG) beta molecule. The other two genes, CGB1 and B2, encode unidentified proteins. We have previously shown that malignant breast transformation is associated with the emergence of the 'trophoblastic' CGB genes (B8, B5 and B3), in addition to the CGB7 gene, which is the only CGB gene expressed in normal breast tissue. To better understand the dysregulation of the CGB/LHB gene cluster in breast cancer, we have developed real-time quantitative RT-PCR assays to analyze each subgroup 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 alpha (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 little if at all), and (iii) not accompanied by overexpression of the CGA gene which is necessary to produce ectopic hCG heterodimeric hormone in breast tumor cells, these latter which yet expressed the LH/CG receptor. These observations suggest that it is mainly the CGB8, B5 and B3 genes which are upregulated in the 19q13.3 CGB gene cluster in breast tumors. They also point to a role (like growth factor) of the CGbeta subunit in breast tumorigenesis, via a novel pathway independent of the LH/CG receptor.