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 carcinoma we have investigated the transcriptional profile of normal mammary gland epithelial cells, cell lines derived from primary tumors, from bone marrow micrometastases and from ascites fluid. mRNA's for ribosomal protein L41 and URIM (Up-Regulated In Metastasis) were consistently increased in all cells derived from metastatic lesions. mRNA for human secreted frizzled-related protein (hsFRP) was found to be dramatically down-regulated in all mammary tumor cells compared to non-transformed mammary gland epithelial cells. mRNA for Human Hypoxia Related Factor--2 (HRF-2) and a transcript including the human mitochondrial control region were significantly overexpressed in the cell lines derived from primary tumors and ascites fluid. A new gene, referred 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 transcript 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 suggest a nuclear localization of the proteins. Surprisingly mRNA for the new gene was detected only in the salivary gland, but not in other adult human tissues and a restricted panel of embryonic tissues. The same holds true for a panel of human tumor cell lines and cell lines derived from ductal mammary carcinoma. RT-PCR revealed expression of PKW in 4 out of 11 breast carcinomas.
Preiherr
J
J
Roche Diagnostics GmbH, Penzberg, Germany.
Hildebrandt
T
T
Klostermann
S
S
Eberhardt
S
S
Kaul
S
S
Weidle
U H
UH
D000595:Amino Acid Sequence; D001483:Base Sequence; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger