Change in expression of basic fibroblast growth factor mRNA in a pituitary tumor clonal cell line.

Abstract

To study pituitary tumor formation, we used a rat pituitary tumor cell line, MtT/E, which was derived from an estrogen-induced rat prolactinoma. MtT/E cells are known not to produce any pituitary hormone; however, they do produce the Pit-1 protein, which is known to be a common transcription factor in thyrotropes, somatotropes, and mammotropes. Although MtT/E is a clonal cell line, it exhibits two distinct phenotypes, fibroblastic (F-) and epithelial (E-) cells. We obtained subclonal cell lines from MtT/E cells with characters similar to those of F- and E-cells and called them MtT/E-G1 and MtT/E-B3, respectively. To examine tumor formation by these cells, we implanted them into female Fischer rats. One month later, typical pituitary tumors had appeared in MtT/E-B3-implanted rats; however, tumor formation by MtT/E-G1 was delayed. Interestingly, the tumors formed by MtT/E-B3 cells were intensely vascularized. To examine changes in tumor cell morphology, we performed primary culture and found that spindle-shaped cells appeared. These spindle-shaped cells were immunopositive for the Pit-1 protein, which suggests that they originated from MtT/E-B3 cells. Interestingly, reverse transcriptase polymerase chain reaction showed that both tumors and the cells obtained in primary culture expressed basic fibroblast growth factor (bFGF). By contrast, the original MtT/E-B3 cells did not express bFGF. These results suggested that MtT/E-B3 cells show a change in phenotype during tumor formation; that is, epithelial-type cells change into bFGFexpressing fibroblastic cells. These phenomena, especially the appearance of bFGFexpressing cells in tumor tissue, may explain the extensive angiogenesis in the tumors formed by MtT/E-B3 cells.