Kong F M, Anscher M S, Washington M K, Killian J K, Jirtle R L
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, NC 27710, USA.
Oncogene. 2000 Mar 16;19(12):1572-8. doi: 10.1038/sj.onc.1203437.
In addition to the intracellular sorting of lysosomal enzymes, the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors. It has also been shown to be mutated in a number of human cancers, and to suppress cancer cell growth. The purpose of this study was to determine if the M6P/IGF2R is mutated in lung cancer, a leading cause of cancer death worldwide. Archival pathology specimens were obtained on 22 patients with newly diagnosed, untreated squamous cell carcinoma of the lung. Two polymorphisms in the 3'-untranslated region of the M6P/IGF2R were used to screen lung tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Nineteen of 22 (86%) patients were informative (heterozygous), and 11/19 (58%) squamous cell carcinomas of the lung had LOH at the M6P/IGF2R locus. The remaining allele in 6/11 (55%) LOH patients contained mutations in either the mannose 6-phosphate or the IGF2 binding domain of the M6P/IGF2R. Thus, the M6P/IGF2R is mutated frequently in squamous cell carcinoma of the lung, providing further support for its function as a tumor suppressor.
除了参与溶酶体酶的细胞内分选外，甘露糖6-磷酸/胰岛素样生长因子II受体（M6P/IGF2R）在调节细胞外蛋白水解酶和生长因子的生物利用度方面也起着关键作用。研究还表明，它在多种人类癌症中发生突变，并能抑制癌细胞生长。本研究的目的是确定M6P/IGF2R在肺癌（全球癌症死亡的主要原因）中是否发生突变。获取了22例新诊断的、未经治疗的肺鳞状细胞癌患者的存档病理标本。利用M6P/IGF2R 3'-非翻译区的两个多态性，通过DNA的PCR扩增来筛查肺肿瘤的杂合性缺失（LOH）。22例患者中有19例（86%）信息充足（杂合子），19例肺鳞状细胞癌中有11例（58%）在M6P/IGF2R位点存在LOH。11例LOH患者中的6例（55%）的剩余等位基因在M6P/IGF2R的甘露糖6-磷酸或IGF2结合域中含有突变。因此，M6P/IGF2R在肺鳞状细胞癌中频繁发生突变，这进一步支持了其作为肿瘤抑制因子的功能。
