We have initiated a series of survey studies of breast and ovarian cancers to determine if specific genes are differentially expressed in those gynecological tumors that go on to metastasize. We are looking specifically at the expression of cell surface receptors such as the 67 kDa high affinity laminin receptor (67LR) and HLBP31 (a 31 kDa laminin binding protein), at genes involved in cell proliferation such as ribonucleotide reductase, as well as genes involved in cell development and differentiation such as homeobox genes. To accomplish this, we have recently cloned the catalytic subunit of human ribonucleotide reductase, HLBP31, and several human homeobox genes from breast cancer cells. Freshly frozen and fixed tumor specimens with matched normal tissue controls are being analyzed at both the protein and RNA levels using specific antibodies and cDNA probes. Western immunoblot, immunohistochemistry, Northern blot, and in situ hybridization techniques are being used to assess specific expression. Results will be correlated with clinical parameters and patient survival to establish the prognostic values of the systematic detection of these genes in gynecological tumors. As an adjunct to these survey studies, in vitro experiments were conducted to determine the specific effect of steroid hormones on human breast cancer cells. In breast cancers, 67 LR and HLBP31 are inversely modulated. The 67LR is upregulated by progesterone in human breast cancer cells. Several polymorphisms/mutations have been detected in homeobox genes in the human breast carcinoma-derived cell line MCF7. The role of these alterations is being examined in breast cancers.
