Abstract

We have approached oral carcinogenesis by initially searching for evidence of activated tyrosine kinases in naturally occurring human neoplasia, especially squamous cell carcinomas of the head and neck. Initial results have shown that the receptor for epidermal growth factor (EGF) is activated in a number of oral cavity tumors. As a probe for the mechanism of this activation, we have investigated the effect of suramin treatment on EGF receptor activity. It was expected that suramin would greatly reduce the level of intracellular protein-tyrosine phosphorylation by the EGF receptor. Instead, the drug dramatically enhanced protein-tyrosine phosphorylation in epithelial cell tumors. The mechanism at play was shown to involve activation of the growth factor, namely transforming growth factor alpha, that in turn stimulates the tyrosine kinase activity of the EGF receptor. These results suggested that suramin may stimulate the growth of certain tumors, and indeed suramin enhances the growth of oral carcinoma cells in culture. Cancer patients receiving suramin chemotherapy currently are being examined for expression of TGFalpha.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000558-01
Application #
3839281
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Nohata, Nijiro; Uchida, Yutaka; Stratman, Amber N et al. (2016) Temporal-specific roles of Rac1 during vascular development and retinal angiogenesis. Dev Biol 411:183-194
Nohata, Nijiro; Abba, Martin C; Gutkind, J Silvio (2016) Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection. Oral Oncol 59:58-66
Doçi, Colleen L; Mikelis, Constantinos M; Lionakis, Michail S et al. (2015) Genetic Identification of SEMA3F as an Antilymphangiogenic Metastasis Suppressor Gene in Head and Neck Squamous Carcinoma. Cancer Res 75:2937-48
Madera, Dmitri; Vitale-Cross, Lynn; Martin, Daniel et al. (2015) Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3. Cancer Prev Res (Phila) 8:197-207
Wang, Zhiyong; Martin, Daniel; Molinolo, Alfredo A et al. (2014) mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. J Natl Cancer Inst 106:
Leelahavanichkul, Kantima; Amornphimoltham, Panomwat; Molinolo, Alfredo A et al. (2014) A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis. Mol Oncol 8:105-18
Coppock, Joseph D; Wieking, Bryant G; Molinolo, Alfredo A et al. (2013) Improved clearance during treatment of HPV-positive head and neck cancer through mTOR inhibition. Neoplasia 15:620-30
Leelahavanichkul, Kantima; Gutkind, J Silvio (2013) Oral and pharyngeal epithelial keratinocyte culture. Methods Mol Biol 945:67-79
Vitale-Cross, Lynn; Molinolo, Alfredo A; Martin, Daniel et al. (2012) Metformin prevents the development of oral squamous cell carcinomas from carcinogen-induced premalignant lesions. Cancer Prev Res (Phila) 5:562-73
Molinolo, Alfredo A; Marsh, Christina; El Dinali, Mohamed et al. (2012) mTOR as a molecular target in HPV-associated oral and cervical squamous carcinomas. Clin Cancer Res 18:2558-68

Showing the most recent 10 out of 96 publications