Transcriptional profiling of human mammary carcinoma cell lines reveals PKW, a new tumor-specific gene

In order to identify genes associated with distinct stages of mammary carci noma we have investigated the transcriptional profile of normal mammary gla nd epithelial cells, cell fines derived from primary tumors, from bone marr ow micrometastases and from ascites fluid. mRNA's for ribosomal protein L41 and URIM (Up-Regulated In Metastasis) were consistently increased in all c ells derived from metastatic lesions. mRNA for human secreted fizzled-relat ed protein (hsFRP) was found to be dramatically down-regulated in all mamma ry tumor cells compared to non-transformed mammary gland epithelial cells m RNA for Human Hypoxia Related Factor-2 (HRF-2) and a transcript including t he human mitochondrial control region were significantly overexpressed in t he cell lines derived from primary tumors and ascites fluid. A new gene, re ferred to as PKW; was only expressed in one of the primary tumor cell lines , the one derived from a medullary carcinoma. The small and the large trans cript which are derived by differential splicing encode potential proteins comprising 95 aa and 130 aa, sharing 88 aa at the N-terminus The IEP's sugg est a nuclear localization of the proteins. Surprisingly mRNA for the new g ene was detected only in the salivary gland, but not in other adult human t issues and a restricted panel of embryonic tissues. The same holds true for a panel of human tumor cell fines and cell lines derived from ductal mamma ry carcinoma. RT-PCR revealed expression of PKW in 4 out of 11 breast carci nomas.