Very few of the genes that are important in
pituitary tumor initiation, progression, and
metastasis have been identified to date. To identify potential genes that may be important in
pituitary tumor progression and
carcinoma development, we used Affymetrix GeneChip HGU-133A-oligonucleotide arrays, which contain more than 15,000 characterized genes from the human genome to study gene expression in an
ACTH pituitary carcinoma metastatic to the liver and four
pituitary adenomas.
Reverse-transcriptase real-time quantitative- PCR (RT-qPCR) was then used to analyze 4 nonneoplastic pituitaries, 19
adenomas, and the
ACTH carcinoma. A larger series of
pituitary adenomas and
carcinomas were also analyzed for
protein expression using tissue microarrays (TMA) (n = 233) and by Western blotting (n = 18). There were 4298 genes that were differentially expressed among the
adenomas compared to the
carcinoma, with 2057 genes overexpressed and 2241 genes underexpressed in the
adenomas. The
beta-galactoside binding protein galactin-3 was underexpressed in some
adenomas compared to the
carcinomas.
Prolactin (PRL) and
ACTH tumors had the highest levels of expression of
galectin-3. The human achaetescute homolog-1 ASCL1 (hASH-1) gene was also underexpressed in some
adenomas compared to the
carcinoma.
Prolactin and
ACTH tumors had the highest levels of expression of hASH-1. ID2, which has an important role in cell development and
tumorigenesis, was underexpressed in some
adenomas compared to the
carcinomas.
Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in
adenomas compared to the
ACTH carcinoma. The differential expression of these genes was validated by RT-qPCR, by immunohistochemistry using TMA and by Western blotting. These results indicate that the
LGALS3, hASH1, ID2, and TLE-4 genes may have important roles in the development of
pituitary carcinomas.