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Characterization of a Novel Tumor-Suppressor Gene PLC1 at 3p22 in Esophageal Squamous Cell Carcinoma

Departments of ¹ Clinical Oncology, ² Pathology, and ³ Anatomy, The University of Hong Kong, Pokfulam, Hong Kong, China; ⁴ Department of Clinical Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China; and ⁵ State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China

Requests for reprints: Xin-Yuan Guan, Department of Clinical Oncology, The University of Hong Kong, Room L10-56, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong. Fax: 852-28169126; E-mail: xyguan{at}hkucc.hku.hk.

Deletion of 3p is one of the most frequent chromosomal alterations in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor-suppressor genes at 3p. Recently, our loss of heterozygosity study revealed that 3p22 was frequently deleted in ESCC and a candidate tumor-suppressor gene (TSG), phospholipase C-1 (PLC1), was identified within the 3p22 region. In this study, absent expression of PLC1 was detected in 26 of 50 (52%) primary ESCCs and 4 of 9 (44.4%) ESCC cell lines, which was significantly associated with DNA copy number loss and promoter hypermethylation (P < 0.05). Functional studies showed that PLC1 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells, including foci formation, colony formation in soft agar, and tumor formation in nude mice. The tumor-suppressive mechanism of PLC1 was associated with its role in the cell cycle arrest at the G₁-S checkpoint by up-regulation of p21 and down-regulation of phosphorylated Akt (Ser⁴⁷³). In addition, down-regulation of PLC1 protein was significantly correlated with ESCC metastasis (P = 0.014), which was associated with its function in increasing cell adhesion and inhibiting cell mobility. Taken together, our results suggest that PLC1 plays an important suppressive role in the development and progression of ESCC. [Cancer Res 2007;67(22):10720–5]

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				Correction: PLC{delta}1 as a Tumor Suppressor in ESCC Cancer Res., May 1, 2008; 68(9): 3549 - 3549. [Full Text] [PDF]