Because we previously found an adenoma with a del(12)(q13q15), we also analyzed normal and tumor DNAs from the 25 tumors separately to identify possible allelic losses at the GLI locus.
The tumor with gli gene amplification lacked the usual histological features of alveolar or embryonal rhabdomyosarcoma; however, ultrastructural analysis of tumor cells established in culture revealed attenuated sarcomeres, resembling those found in primitive rhabdomyoblasts.
The predicted proteins probably control the expression of other genes and, by analogy with Kr and GLI, may be important in human development, tissue-specific differentiation, or neoplasia.
Here we show that ectopic expression of the zinc-finger transcription factor Gli1 in the embryonic frog epidermis results in the development of tumours that express endogenous Gli1.
These findings firmly establish that increased GLI-1 expression is central and probably sufficient for tumor development and suggest that GLI-1-induced tumor development does not depend on additional p53 or Ha ras mutations.
The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway.
We also show that a variety of primary human brain tumors and tumor lines consistently express the GLI genes and that cyclopamine, a SHH signaling inhibitor, inhibits the proliferation of tumor cells.
Additional investigation by reverse transcription-polymerase chain reaction in four basal cell carcinomas and two nevus sebaceous tumors also showed the expression of Gli-1, another target gene in the patched-hedgehog signaling pathway, in all the basal cell carcinomas samples but not in any of the nevus sebaceous tumors examined.
In contrast, there was no significant correlation between the mRNA levels of the Gli family members and histological malignancy, suggesting that Gli proteins are not associated with the progression of astrocytic tumors.
As BCCs have been proposed to originate from the ORS, loss of PKCalpha expression may be relevant to tumor formation; this may, in part, be because of the predicted increase in Gli1 transcriptional activity.
Shh expressed by LNCaP tumor cells activates Gli-1 expression in the tumor stroma, 2). genetically engineered Shh overexpression in LNCaP cells leads to increased tumor stromal Gli-1 expression, and 3).
Mutational inactivation of the tumor suppressor gene patched (PTCH) leads to constitutive activation of the Hh signaling pathway, resulting in activation of target gene transcription by the zinc finger transcription factors GLI1 and GLI2.
In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75NTR or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer.
While the sonic hedgehog (Shh) transcript is localized to the tumor tissue, expression of Gli1 and PTCH1 is observed both in the tumor and in the stroma.
We identify two independent destruction signals in Gli1, D(N) and D(C), and show that removal of these signals stabilizes Gli1 protein and rapidly accelerates tumor formation in transgenic animals.
Interestingly, GLI1 was expressed in most SCLC tumors studied, indicating that HH signaling is important for in vivo growth of SCLC but establishment of cell lines from SCLC tumors may lead to loss of expression of key HH pathway members.
Constitutive activation of the hedgehog pathway is implicated in the development of many human malignancies; hedgehog targets, PTCH1 and Gli1, are markers of hedgehog signaling activation and are expressed in most hedgehog-associated tumors.
Parathyroid hormone-related protein regulates glioma-associated oncogene transcriptional activation: lessons learned from bone development and cartilage neoplasia.
We show that SHH, but not its transcriptional effector GLI1, is amplified in ALK+ ALCL tumors and cell lines, and that SHH and GLI1 proteins are highly expressed in ALK+ ALCL tumors and cell lines.
One particular miRNA (miRNA Gli-1-3548) and its corresponding duplex (Duplex 3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells by delaying cell division and activating late apoptosis in MiaPaCa-2 cells.