The number of dogs developing tumours of the prostate is currently increasing. Furthermore the dog is -beside humans- the only known mammalian species that spontaneously develops this locally invasive disease with a high metastatic potential. Both species show striking similarities in the development and progress of the disease: Prostate carcinoma most commonly appear in older patients, the tumours are likely to metastasise to distant regions by blood or lymphatic system, and the tumours vary with respect to their clinical behaviour. Molecular indicators allowing for a valid prognosis of these cancers are of considerable interest, because based on the histology of the lesions alone it is often not possible to recognize sufficiently the malignant potential of the tumour in terms of local invasiveness and metastatic spread.
HMGA proteins are members of the High-Mobility-Group family of proteins which normally are expressed during embryonic development and are down-regulated in adult tissues. Currently there are three well known members of the HMGA family: HMGA1a and HMGA1b, deriving from alternatively spliced mRNAs of the same gene and HMGA2, which is encoded by a separate gene. Due to their ability to mediate the binding of other transcription factors without transcriptional activity per se, HMGA-proteins are called architectural transcriptions factors. In human carcinomas the overexpression or aberrant expression often correlates with the degree of neoplastic cell transformation and metastatic tumour progression. In tissue specific cell-lines, the application of an adenovirus carrying the HMGA1 gene in antisense orientation abrogated the effects mediated by over expression of HMGA1. Taken together HMGA expression is considered as a possible molecular marker in prostate cancer diagnosis.
HMGA proteins are highly conserved during evolution. In previous investigations we were able to demonstrate the existence of HMGA genes in the canine genome as well as the close similarity between canine and human genes and proteins. In the present study we have determined the HMGA2 expression patterns by real-time quantitative RT-PCR in prostatic tissues from 16 dogs with diverse histological findings. The study includes 4 samples of non-neoplastic tissues, 3 hyperplasias, 3 cysts, and 6 carcinomas. The results show that expression of HMGA2 is highest in carcinomas, less intense in benign neoplasms with intermediate values for cysts and hyperplasias and is markedly low in non-neoplastic tissues. Actually, there is a 19-fold divergence in expression between the highest transcript level of non-neoplastic tissues and the lowest transcript level observed in carcinomas. In our study all malignant neoplasias showed expression levels beyond 50,000 transcripts per 250 ng total RNA, whereas none of the non-malignant tissues showed expression levels above this value. These results indicate that HMGA2 indeed may serve as a molecular marker in prostate cancer diagnosis.