Study of the molecular mechanisms of betel quid-induced oral squamous cell carcinoma (OSCC)

Autor: Jeff Chen, 陳逸夫
Rok vydání: 2004
Druh dokumentu: 學位論文 ; thesis
Popis: 92
Betel quid (BQ) chewing has been widely practiced in many parts of Southeast Asian countries and Asian-migrant communities elsewhere, adding up to a total of 600 million BQ chewers globally. In Taiwan BQ chewing is also a prevalent habit especially in the male population, which accounts for the increased risk of oral squamous cell carcinoma (OSCC). In an attempt to gain better insights into the molecular mechanisms underlying BQ-induced OSCC, we fortuitously identified a scaffold protein, microtubule-associated protein 2 (MAP2), was highly induced by BQ extract in cultured normal human oral keratinocytes (NHOKs). We then confirmed induction of MAP2 at both RNA and protein levels, followed by investigation of expression of MAP2 in human oral tissues including normal mucosa, leukoplakia and OSCC that are clinicopathologically corresponding to normal, premalignant and malignant, respectively, in the presence or absence of BQ exposure. Our results demonstrated a significant correlation between MAP2 expression and progression of BQ-induced carcinogenesis. In addition, we have provided evidence that expression and tyrosine phosphorylation of MAP2, presumably by the Src family tyrosine kinases, is likely to play a direct role in regulating BQ-induced cell migration. Taken together, these findings potentiate MAP2 or MAP2-tethered cellular signaling pathways therapeutic targets for BQ-chewing OSCC.
Databáze: Networked Digital Library of Theses & Dissertations