This Article Full Text Full Text (PDF) Correction (v13,p6543) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shao, L. Articles by Tao, Q. Search for Related Content PubMed PubMed Citation Articles by Shao, L. Articles by Tao, Q.

CMTM5 Exhibits Tumor Suppressor Activities and Is Frequently Silenced by Methylation in Carcinoma Cell Lines

Authors' Affiliations: ¹ Peking University Center for Human Disease Genomics, 35 Xueynun Road, Beijing, 100083, China; ² Cancer Epigenetics Laboratory, State Key Laboratory in Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China

Requests for reprints: Dalong Ma, Peking University Center for Human Disease Genomics, 38 Xueyuan Road, Beijing 100083, China. Phone: 86-10-8280-1149; Fax: 86-10-8280-1149; E-mail: madl{at}bjmu.edu.cn or Qian Tao, Room 315, Cancer Center, PWH, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, Hong Kong. Phone: 852-2632-1340; Fax: 852-2848-8842; E-mail: qtao{at}clo.cuhk.edu.hk.

Purpose: CMTM5 (CKLF-like MARVEL transmembrane domain containing member 5) is located at 14q11.2, a locus associated with multiple cancers. It has six RNA splicing variants with CMTM5-v1 as the major one. We explored its expression pattern in normal tissues and tumor cell lines, as well as its functions in carcinoma cells.

Experimental Design: We evaluated CMTM5 expression by semiquantitative reverse transcription-PCR (RT-PCR) in normal tissues and carcinoma cell lines of cervical, breast, nasopharyngeal, lung, hepatocellular, esophageal, gastric, colon, and prostate. We further examined CMTM5 promoter methylation in these cell lines. We also analyzed CMTM5 expression after 5-aza-2'-deoxycytidine treatment and genetic demethylation and the functional consequences of restoring CMTM5 in HeLa and PC-3 cells.

Results: CMTM5-v1 is broadly expressed in human normal adult and fetal tissues, but undetectable or down-regulated in most carcinoma cell lines. Its promoter methylation was detected in virtually all the silenced or down-regulated cell lines. The silencing of CMTM5 could be reversed by pharmacologic demethylation or genetic double-knockout of DNMT1 and DNMT3B, indicating methylation-mediated mechanism. Restoration of CMTM5-v1 suppressed carcinoma cell proliferation, migration, and invasion.

Conclusions: These results indicate that CMTM5 exhibits tumor suppressor activities, but with frequent epigenetic inactivation in carcinoma cell lines.