Correlation between fatty acid synthase, and proteins involved in cell cycle and angiogenesis with human malignant melanoma prognosis

• Grant number: 12/13834-4
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2012 - October 31, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Karina Gottardello Zecchin
• Grantee: Karina Gottardello Zecchin
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid, palmitate. In contrast to most normal cells, FASN is overexpressed in a variety of human cancers, including cutaneous melanoma, in which its levels of expression are associated with tumor invasion and poor prognosis. We have previously shown that FASN inhibition reduces proliferation and promotes apoptosis in B16-F10 mouse melanoma cells, and decrease their metastatic spread in orlistat-treated C57BL6 mice bearing intraperitoneal melanomas (Carvalho et al., 2008). We also demonstrated that FASN inhibition in B16-F10 melanoma cells (i) induces the intrinsic pathway of apoptosis, as demonstrated by the cytochrome c release and caspases-9 and -3 activation (Zecchin et al., 2010), (ii) induces cell cycle arrest by accumulation of the tumor suppressor proteins p21WAF1/Cip1 and p27Kip1 co-immunoprecipitated with cdk2, together with decreased amounts of cdk2 and Skp2, and (iii) modifies the free fatty acid composition of mitochondria (Zecchin et al., 2011). The aim of this work is to analyze the expression of FASN, cell cycle proteins such p21WAF1/Cip1, p27Kip1, p16Ink4a, Cdk-4, and Rb, as well as VEGF165b and HIF-1± in human malignant melanoma samples by immunohistochemistry. Further, a possible correlation of these results with clinical and histological findings will be checked, in order to collaborate with human malignant melanoma prognosis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOARES, CIRO D.; BORGES, CAMILLA F.; SENA-FILHO, MARCONDES; DE ALMEIDA, OSLEI P.; STELINI, RAFAEL F.; CINTRA, MARIA L.; GRANER, EDGARD; ZECCHIN, KARINA G.; JORGE, JACKS. Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas. Melanoma Research, v. 27, n. 5, p. 448-456, OCT 2017. (13/25305-9, 15/25905-1, 12/14008-0, 12/13834-4)

GOMES, CAMILLA B. F.; ZECHIN, KARINA G.; XU, SHUYUN; STELINI, RAFAEL F.; NISHIMOTO, INES N.; ZHAN, QIAN; XU, TING; QIN, GUNGWEI; TREISTER, NATHANIEL S.; MURPHY, GEORGE F.; et al. TET2 Negatively Regulates Nestin Expression in Human Melanoma. American Journal of Pathology, v. 186, n. 6, p. 1427-1434, JUN 2016. (12/14008-0, 12/13834-4)