Down-regulation of tumor suppressor gene FEZ1/LZTS1 in breast carcinoma involves promoter methylation and associates with metastasis.
FEZ1/LZTS1 is a tumor suppressor gene located in chromosomal band 8p22, and methylation has been identified as a mechanism for its loss of function in tumors. Chromosomal deletion at 8p22 is also frequent in breast cancer. We therefore examined whether LZTS1 plays a role in breast cancer. We analyzed expression of LZTS1 at both the RNA and protein levels, and promoter methylation in a number of primary tumors and cell lines from breast cancer. We also examined the association between LZTS1 expression and different clinicopathological parameters of breast cancer. We found that the expression of LZTS1 mRNA was reduced in 25 of 50 (50%) primary tumors and 29 of 30 (97%) breast cancer cell lines. Immunohistochemical staining showed that LZTS1 protein was absent or down-regulated in 72 (72%) of 100 primary breast carcinomas. Reduced expression of LZTS1 at either the RNA or protein level was significantly correlated with lymph node metastases (P < 0.05). DNA methylation analysis revealed that the LZTS1 gene was frequently methylated in both cell lines and primary tumors from breast cancer, and the extent of DNA methylation was correlated with reduced expression of the gene. These findings suggest that LZTS1 plays a role in the development and progression of breast cancer at least through promoter methylation-mediated transcriptional downregulation.
Chen
Ling
L
Department of Breast Cancer Pathology, Key Laboratory of Breast Cancer Research, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China.
Zhu
Zhengmao
Z
Sun
Xiaodong
X
Dong
Xue-Yuan
XY
Wei
Jia
J
Gu
Feng
F
Sun
Yu-Lan
YL
Zhou
Jun
J
Dong
Jin-Tang
JT
Fu
Li
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; C509917:LZTR1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors