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CMTM3 在肾透明细胞癌中经常缺失,并表现出肿瘤抑制活性。

CMTM3 is frequently reduced in clear cell renal cell carcinoma and exhibits tumor suppressor activities.

机构信息

Department of Urology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.

出版信息

Clin Transl Oncol. 2014 Apr;16(4):402-9. doi: 10.1007/s12094-013-1092-3. Epub 2013 Aug 2.

Abstract

PURPOSE

CKLF-like MARVEL transmembrane domain containing member 3 (CMTM3) is silenced in many kinds of cancers and inhibits tumor cells growth. We investigated the expression and role of CMTM3 in clear cell renal cell carcinoma (ccRCC).

METHODS

The expression of CMTM3 was detected in ccRCC tissue microarray, specimens, and cell lines by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. After transfected with CMTM3 plasmid or vector, the proliferation and migration of ccRCC 786-0 cells were determined by MTT assay and transwell assay, respectively. Furthermore, the anchorage-independent growth of transfected cells was assessed using soft agar colony formation assay.

RESULTS

CMTM3 was down-regulated in 84 % (63/75) of ccRCC tissues and its expression had no correlation with the gender, age, clinical staging and histologic grade. CMTM3 protein was undetectable by western blot in most detected ccRCC specimens and two RCC cell lines (786-0 and ACHN). qRT-PCR analysis showed that CMTM3 mRNA was dramatically down-regulated in 40 ccRCC cancer tissues as compared with the paired adjacent normal ones. Restoration of CMTM3 significantly suppressed the anchorage-independent growth, proliferation and migration of 786-0 cells.

CONCLUSION

These results indicate that CMTM3 is significantly down-regulated in ccRCC and exerts remarkable tumor-suppressive functions in 786-0 cells. Reduction of CMTM3 expression may contribute to the pathogenesis of ccRCC and CMTM3 may be a potentially target for therapeutic strategy.

摘要

目的

CKLF 样 MARVEL 跨膜结构域包含成员 3(CMTM3)在许多类型的癌症中被沉默,并抑制肿瘤细胞生长。我们研究了 CMTM3 在透明细胞肾细胞癌(ccRCC)中的表达和作用。

方法

通过免疫组织化学、实时定量聚合酶链反应(qRT-PCR)和 Western blot 分别检测 CMTM3 在 ccRCC 组织微阵列、标本和细胞系中的表达。转染 CMTM3 质粒或载体后,通过 MTT 测定和 Transwell 测定分别测定 ccRCC 786-0 细胞的增殖和迁移。此外,通过软琼脂集落形成测定评估转染细胞的锚定非依赖性生长。

结果

CMTM3 在 84%(63/75)的 ccRCC 组织中下调,其表达与性别、年龄、临床分期和组织学分级无关。Western blot 在大多数检测的 ccRCC 标本和两个 RCC 细胞系(786-0 和 ACHN)中均未检测到 CMTM3 蛋白。qRT-PCR 分析显示,与配对的相邻正常组织相比,40 个 ccRCC 癌组织中 CMTM3 mRNA 显著下调。CMTM3 的恢复显著抑制了 786-0 细胞的锚定非依赖性生长、增殖和迁移。

结论

这些结果表明,CMTM3 在 ccRCC 中显著下调,并在 786-0 细胞中发挥显著的肿瘤抑制功能。CMTM3 表达的降低可能有助于 ccRCC 的发病机制,CMTM3 可能是一种潜在的治疗策略靶点。

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