TY - JOUR
T1 - The p53-family members p63 and p73 inhibit insulin-like growth factor-I receptor gene expression in colon cancer cells
AU - Nahor, Irit
AU - Abramovitch, Shirley
AU - Engeland, Kurt
AU - Werner, Haim
N1 - Funding Information:
This work was performed in partial fulfillment of the requirements for an M.Sc. degree by Irit Nahor in the Sackler Faculty of Medicine, Tel Aviv University. We thank Drs. Hua Lu and Bert Vogelstein for cell lines and reagents. K.E. is supported by grants from the Interdisciplinary Center for Clinical Research (IZKF) at the University of Leipzig and the Deutsche Forschungsgemeinschaft.
PY - 2005/12
Y1 - 2005/12
N2 - The insulin-like growth factor-I receptor (IGF-IR) has a critical role in malignant transformation. Consistent with its antiapoptotic role, the IGF-IR gene is overexpressed in most types of cancer, including colorectal tumors. The recently identified p53 homologues, p63 and p73, exhibit some of the biological properties of p53, including the ability to transactivate p53-responsive genes and to induce apoptosis. In the present study, we examined the hypothesis that p63/p73 proteins may contribute to colon cancer cell proliferation via mechanism/s that involve regulation of IGF-IR gene expression. Using transient co-expression assays in colon cancer-derived HCT116 cells, we showed that both proteins inhibit IGF-IR promoter activity and endogenous IGF-IR levels in a dose-dependent manner, whereas mutant proteins are significantly impaired in their ability to suppress IGF-IR gene expression. These results are compatible with the notion that disruption of p63/p73-mediated signal transduction pathways in colon cancer may lead to increased IGF-IR gene transcription. In summary, we have identified the IGF-IR gene as a novel downstream target for p63/p73 action.
AB - The insulin-like growth factor-I receptor (IGF-IR) has a critical role in malignant transformation. Consistent with its antiapoptotic role, the IGF-IR gene is overexpressed in most types of cancer, including colorectal tumors. The recently identified p53 homologues, p63 and p73, exhibit some of the biological properties of p53, including the ability to transactivate p53-responsive genes and to induce apoptosis. In the present study, we examined the hypothesis that p63/p73 proteins may contribute to colon cancer cell proliferation via mechanism/s that involve regulation of IGF-IR gene expression. Using transient co-expression assays in colon cancer-derived HCT116 cells, we showed that both proteins inhibit IGF-IR promoter activity and endogenous IGF-IR levels in a dose-dependent manner, whereas mutant proteins are significantly impaired in their ability to suppress IGF-IR gene expression. These results are compatible with the notion that disruption of p63/p73-mediated signal transduction pathways in colon cancer may lead to increased IGF-IR gene transcription. In summary, we have identified the IGF-IR gene as a novel downstream target for p63/p73 action.
KW - Colorectal cancer
KW - IGF
KW - IGF-I receptor
KW - Transcription
KW - p53
KW - p63
KW - p73
UR - http://www.scopus.com/inward/record.url?scp=28044468153&partnerID=8YFLogxK
U2 - 10.1016/j.ghir.2005.07.005
DO - 10.1016/j.ghir.2005.07.005
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C2 - 16181796
AN - SCOPUS:28044468153
SN - 1096-6374
VL - 15
SP - 388
EP - 396
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 6
ER -
