Hibi K, Yamakawa K, Ueda R, Horio Y, Murata Y, Tamari M, Uchida K, Takahashi T, Nakamura Y, Takahashi T
Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Oncogene. 1994 Feb;9(2):611-9.
Our recent identification of homozygous deletions at 3p21.3 in lung cancer has provided further support for the presence of a tumor suppressor gene in this chromosomal region. As a part of our efforts for positional cloning of a tumor suppressor gene at 3p21.3, we have characterized a transcriptional unit within this region using genomic fragments with interspecies conservation. The identified gene was found to encode a novel integrin alpha subunit, termed alpha RLC, which is closely related to alpha 4 in structure but clearly different from alpha 4 in its expression pattern in the physiological and pathological setting of the lung. This finding and the exact localization of the gene suggest that it is a good candidate for a tumor suppressor gene in lung cancer, but our extensive search covering one third of the gene did not reveal any somatic mutations within the coding region. Interestingly, however, alpha RLC was abundantly expressed in fetal lung and lung cancers, particularly small cell lung cancers (SCLC). Its aberrant upregulation in the SCLC samples, both cell lines and primary tumors, which might have been caused by a yet unidentified mutations or by deletions of other gene, and its homology to alpha 4, which is thought to play a role in metastasis, suggest that altered alpha RLC expression may contribute to the acquisition of malignant phenotypes of this type of lung cancer.
我们最近在肺癌中鉴定出3p21.3处的纯合缺失，这为该染色体区域存在肿瘤抑制基因提供了进一步支持。作为我们在3p21.3位置克隆肿瘤抑制基因工作的一部分，我们利用具有种间保守性的基因组片段对该区域内的一个转录单元进行了特征分析。发现所鉴定的基因编码一种新型整合素α亚基，称为αRLC，其在结构上与α4密切相关，但在肺的生理和病理环境中的表达模式与α4明显不同。这一发现以及该基因的确切定位表明它是肺癌肿瘤抑制基因的一个良好候选者，但我们对该基因三分之一区域的广泛搜索并未在编码区内发现任何体细胞突变。然而，有趣的是，αRLC在胎儿肺和肺癌中大量表达，尤其是小细胞肺癌（SCLC）。它在SCLC样本（细胞系和原发性肿瘤）中的异常上调，可能是由尚未鉴定的突变或其他基因的缺失引起的，以及它与α4的同源性，α4被认为在转移中起作用，这表明αRLC表达的改变可能有助于这种类型肺癌获得恶性表型。
