A role for the pituitary tumor-transforming gene in the genesis and progression of non-small cell lung carcinomas.
BACKGROUND
The product of the pituitary tumor-transforming gene (PTTG) inhibits chromatid separation, which is considered to promote chromosome instability, especially in the absence of the p53 gene product, and also induces basic fibroblast growth factor (bFGF) production. Its expression and these variables in primary non-small cell carcinomas (NSCLCs) of known p53 status were examined.


METHODS
Comparative genomic hybridization analysis of 78 lesions revealed a wide range of total (gain + loss) chromosomal imbalance numbers (tCINs). Seven each with the highest and lowest tCINs were examined for PTTG mRNA by semi-quantitative RT-PCR and bFGF production immunohistochemically.


RESULTS
Mean relative values for PTTG mRNA for the tumors and corresponding normal lung tissues were 1.46 and 0.88, respectively, the difference being statistically significant. Overexpression of bFGF was observed in 12 out of 14 with intense immunostaining of carcinoma cells, in contrast to the weak or lack of staining in normal lung tissues. However, relative PTTG values did not correlate with tCINs or immunoreactivity for bFGF among the tumors regardless of the p53 status.


CONCLUSIONS
The results indicate that overexpression of PTTG plays a role in the genesis and progression of NSCLCs, although its effects on CINs and bFGF production may be obscured by other complicating factors.
Honda
Shoko
S
Cancer Diagnosis Group, Saitama Cancer Center Research Division, 818 Ina-machi, Kita-adachi-gun, Saitama 362-0806, Japan.
Hayashi
Moriaki
M
Kobayashi
Yasuhito
Y
Ishikawa
Yuichi
Y
Nakagawa
Ken
K
Tsuchiya
Eiju
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D064249:Securin
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016222:Fibroblast Growth Factor 2