Evaluation of Messenger RNA of Pituitary Tumour-transforming Gene-1 (PTTG1) as a Molecular Marker for Micrometastasis.

Pituitary tumor-transforming gene-1 (PTTG1) has been implicated as an inhibitor of chromatid separation; its overexpression may lead to chromosomal instability. PTTG1 functions through SH3-mediated signal transduction pathways and activation of growth factors, including basic fibroblast growth factor (bFGF) mediated-angiogenesis. In order to detect micrometastasis in solid tumor patients, we developed a model system based on reverse transcriptase (RT)-PCR amplification of PTTG1 mRNA. We analyzed PTTG1 expression, using RT-PCR, in a panel of human tumors cell-lines (hTCL), including breast, gastrointestinal, small-cell lung cancer, and haematopoietic neoplasms. In addition, to newly hTCL established in our laboratory were investigated: Pancreatic, MBQ-OJC1. Small cell lung carcinoma, JCA-OJC3. Colon, JJPF-OJC4. Specific amplicon for PTTG1 was confirmed by RT-PCR in all the hTCL tested. In breast cell lines expression for PTTG1-mRNA was not related to invasiveness, tumorogenicity, or estrogen receptor (ERα) status. PTTG1-mRNA was examined by PCR amplification of cDNA obtained from normal lymph nodes, bone marrow, and peripheral blood (cellular and plasmatic mRNA). Using a hot-start PCR and different amounts of input RNA, PTTG1 transcript was detected in control bone marrow but not on lymph nodes. PTTG1-mRNA was detected in peripheral blood from 4/14 healthy donors analyzed. Our data confirms that PTTG1 is abundantly expressed in human tumors of different histologic types. PTTG1 qualitative mRNA detection may be useful as a surrogate molecular marker for angiogenic phenotype and invasive tumor, however, it is not useful as a micrometastasis marker due to its transcription in normal bone marrow and peripheral blood. [ABSTRACT FROM AUTHOR]