Epigenetic inactivation of RASSF14 in lung and breast cancers and malignant phenotype suppression

Dg. Burbee et al., Epigenetic inactivation of RASSF14 in lung and breast cancers and malignant phenotype suppression, J NAT CANC, 93(9), 2001, pp. 691-699
Citations number
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Year of publication
691 - 699
SICI code
Background: The recently identified RASSF1 locus is located within a 120-ki lobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers. Methods: We assessed exp ression of two RASSF1 gene products, RASSF1A and RASSF1C, and the methylati on status of their respective promoters in 27 non-small-cell lung cancer (N SCLC) cell lines, in 107 resected NSCLCs, in 47 small-cell Lung cancer (SCL C) cell lines, in 22 breast cancer cell lines, in 39 resected breast cancer s, in 104 nonmalignant lung samples, and in three breast and lung epithelia l cultures, We also transfected a lung cancer cell line that lacks RASSF1A expression with vectors containing RASSF1A complementary DNA to determine w hether exogenous expression of RASSF1A would affect in vitro growth and in vivo tumorigenicity of this cell line. Ail statistical tests were two-sided . Results: RASSF1A messenger RNA was expressed in nonmalignant epithelial c ultures but not in 100% of the SCLC, in 65% of the NSCLC, or in 60% of the breast cancer lines. By contrast, RASSF1C was expressed in all nonmalignant cell cultures and in nearly all cancer cell lines. RASSF1A promoter hyperm ethylation was detected in 100% of SCLC, in 63% of NSCLC, in 63% of breast cancer lines, in 30% of primary NSCLCs, and in 39% of primary breast tumors but in none of the nonmalignant lung tissues, RASSF1A promoter hypermethyl ation in resected NSCLCs was associated with impaired patient survival (P = .046), Exogenous expression of RASSF1A in a cell line lacking expression de creased in vitro colony formation and in vivo tumorigenicity. Conclusion: R ASSF1A is a potential tumor suppressor gene that undergoes epigenetic inact ivation in lung and breast cancers through hypermethylation of its promoter region.