Abstract Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide 3-kinase (PI3K) pathway, LY294002, or with small interfering RNA (siRNA) targeting STAT3. Thus, our study identified the EGF/PI3K/STAT3 signaling as an essential pathway regulating VEGF and leptin expression in EGF-responsive colon cancer cells. This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti-EGF receptor drugs are ineffective.

Cascio, S., Ferla, R., D'Andrea, A., Gerbino, A., Bazan, V., Surmacz, E., et al. (2009). Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells. JOURNAL OF CELLULAR PHYSIOLOGY, 221 [10.1002/jcp.21843].

Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.

GERBINO, Aldo;BAZAN, Viviana;RUSSO, Antonio
2009-01-01

Abstract

Abstract Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide 3-kinase (PI3K) pathway, LY294002, or with small interfering RNA (siRNA) targeting STAT3. Thus, our study identified the EGF/PI3K/STAT3 signaling as an essential pathway regulating VEGF and leptin expression in EGF-responsive colon cancer cells. This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti-EGF receptor drugs are ineffective.
2009
Cascio, S., Ferla, R., D'Andrea, A., Gerbino, A., Bazan, V., Surmacz, E., et al. (2009). Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells. JOURNAL OF CELLULAR PHYSIOLOGY, 221 [10.1002/jcp.21843].
File in questo prodotto:
File Dimensione Formato  
VEGF - Leptin 2009.pdf

accesso aperto

Dimensione 231.5 kB
Formato Adobe PDF
231.5 kB Adobe PDF Visualizza/Apri
Expression of angiogenic regulators, VEGF and leptin, is regulated by the.pdf

accesso aperto

Dimensione 231.5 kB
Formato Adobe PDF
231.5 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/42638
Citazioni
  • ???jsp.display-item.citation.pmc??? 23
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 40
social impact