Department of Urology, The first affiliated hospital, ChongQing Medical University, 1 YouYi Road, Central District, ChongQing 400016, China.
BMC Cancer. 2010 Mar 8;10:83. doi: 10.1186/1471-2407-10-83.
The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).
HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.
HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.
HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.
hepaCAM 基因编码一种新的免疫球蛋白样细胞黏附分子，其表达在多种人类癌症中受到抑制。此外，hepaCAM 具有通常在肿瘤抑制基因中观察到的特性。然而，hepaCAM 在膀胱癌中的表达和生物学功能尚未得到研究。因此，我们试图研究 hepaCAM 在人膀胱移行细胞癌（TCCB）中的表达及其结构与功能的关系。
采用半定量 RT-PCR 法检测 28 例正常膀胱组织和 34 例 TCCB 膀胱标本及 2 株 TCCB 细胞系中 hepaCAM 的表达。将野生型 hepaCAM 和胞外结构域缺失型突变基因转染至 TCCB 细胞系 T24，评估野生型基因和结构域缺失型突变体的生物学特性。
在 34 例 TCCB 标本中，82%（28/34）的 hepaCAM 表达下调，在 2 株检测的 TCCB 细胞系中均未检测到 hepaCAM 的表达。T24 细胞中 hepaCAM 的定位似乎依赖于细胞密度。在广泛分散的细胞中，hepaCAM 聚集在核周膜和细胞表面突起处，而在细胞融合的细胞中，hepaCAM 主要定位于细胞膜上细胞-细胞接触部位。功能上，表达 hepaCAM 不仅增加了细胞铺展、延迟了细胞脱落、增强了伤口愈合和促进了细胞侵袭，而且还抑制了细胞生长（P < 0.01）。当缺失胞外结构域时，hepaCAM 的定位明显改变，丧失了黏附功能及其对细胞生长的影响。
hepaCAM 参与细胞黏附和生长调控，其在 TCCB 中常被沉默。hepaCAM 的胞外结构域对其生理和生物学功能至关重要。
