Differential gene expression in benign and malignant human breast tumours.

Metastasis is a complex process involving the dissemination of tumour cells from the site of the primary tumour and their subsequent growth at a distant site. Metastasis is the major cause of death in breast cancer patients, and so the elucidation of molecular mechanisms of metastasis is a major goal in cancer research today. Two types of tumour which differ in their metastatic capacities were compared in an attempt to identify those genes which are associated with the malignant phenotype. Differential screening of cDNA libraries from fibroadenomas (benign) and carcinomas (malignant) of the breast was used to identify sequences corresponding to genes expressed at different levels in these two tissues. Expression of the sequences identified was predominantly in the epithelium of the tumour samples, as shown by in situ hybridisation, and the sequences fell into three groups. A number of transcripts of the mitochondrial genome were found to be more abundant in carcinoma samples, including subunit 2 of cytochrome c oxidase, subunits 2 and 4 of NADH dehydrogenase, and subunit 6 of F0F1ATPase, although the abundances of the latter three sequences were not significantly different when a larger panel was examined. Conversely, a group of translation-associated transcripts were found to be more abundant in fibroadenomas. The mRNAs corresponding to elongation factor 1? and the ribosomal protein P2 were more abundant in the benign tissue studied. This finding correlates positively with the higher levels of expression in fibroadenomas of another ribosomal protein (HUBCEP80) in the panel of tumours studied here. Similarly, differential screening indicates that the third group of sequences are more abundant in fibroadenomas relative to carcinomas. This group contains interspersed repetitive elements of the Alu family.