Breast cancer is the most common form of solid malignancy in women. One in nine women will develop breast cancer and about 30% of them will ultimately die from the disease. Although lymph node status, steroid receptor status and ploidy are statistically predictive, they are often poor prognosticators for individual patients. Many other factors associated with molecular changes in cancer progression have been evaluated; for example, oncogene activation (c-erbB2, c-myc, int2) and tumor-suppressor gene inactivation (Rb and p53). All these molecular changes have been found to be associated to a certain degree to the different breast cancer phenotypes, but their clinical value is still far from a feasible application. To develop valid diagnostic and prognostic markers, with the goal of identifying genes that are activated or inactivated in the multistep carcinogenesis of breast cancer, we have used two very powerful approaches, the differential display and subtraction hybridization to clone novel genes. We used mRNAs derived from cancer and normal breast cell lines (HTB-126 and HTB-125, respectively) and have isolated a large number of genes. By DNA sequence analysis and homology search, we have found that several of these genes are unique and have not thus far been identified in any gene bank. Several of the novel genes were examined by Northern blot analysis and they showed marked differential mRNA expression in normal and cancer cell lines, and in normal and tumor samples derived from breast tissues. One of the genes (BCS1) shows limited homology with the insulin-like growth factor binding protein, IGFBP-1. So far, six IGFBPs have been cloned and characterized. It appears that the BCS1 represents a new, novel member of the IGFBP family. Similar to IGFBPs, BCS1 may modulate the function of insulin-like growth factors (IGF-I and IGF-II) and play an important role in the interaction between IGFs and their receptors during cell growth.
