Endocrine Abstracts

Background. The GH/IGF-I axis has been implicated in the pathogenesis of colon and breast cancer. We have recently demonstrated that the local expression of its components correlates with that of tumour-associated genes and angiogenesis. The two predominant isomers of GH in humans are 22kDa and 20kDa isomers. A recent study reported that the two isomers exert opposing effects on breast cancer cells: 22kDa GH promotes proliferation whereas 20kDa GH inhibits proliferation. The local expression of these isomers in the breast and colon is unknown.

Aim. To determine the mRNA expression of 22 kDa and 20 kDa GH in normal and malignant colon and breast tissue.

Methods. The mRNA levels of 22kDa and 20kDa GH were quantified by RT-PCR ('Taqman') assays on paired samples of normal (N) and malignant (T) breast (n=15) and colon (n=33) tissue. Specific primers were designed for the two isomers that either spanned or skipped the mRNA sequence that is present in 22kDa transcripts and absent in 20kDa transcripts. Results were expressed as copy number per microgram of total RNA.

Results. 22kDa GH was expressed in all breast samples (median copy number 7.87 x 104 vs 15.2 x 104 for N and T samples respectively. However, 20kDa GH was absent in 14/15 N and 11/15 T breast samples. In the colon, 22kDa GH was expressed in 31/33 N and all T samples (median copy numbers similar). 20kDa GH was absent in 19/33 N and 14/33 T samples. Median copy numbers in those expressing 20kDa GH were 2.04 x 104 and 2.25 x 104 for N and T samples respectively.

Conclusion. The predominant form of GH mRNA in breast and colon tissue is the 22kDa isomer, a promoter of cellular proliferation. The lack of 20kDa GH mRNA, a reported anti-proliferative isomer, may be implicated in the pathogenesis of colon and breast cancer.