Laws S A, Gough A C, Evans A A, Bains M A, Primrose J N
University Department of Surgery, Southampton General Hospital, Hampshire, UK.
Br J Cancer. 1997;75(3):360-6. doi: 10.1038/bjc.1997.59.
Somatostatin analogues may be useful novel agents in the systemic treatment of advanced colorectal cancer, as somatostatin inhibits proliferation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour and mucosal samples respectively, but in 75% (9/12) of early-stage tumours (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) of late-stage tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (chi2 with Yates' correction). There was also reduced expression of hSSTR5 in samples of metastatic tumour (11%, 1/9) compared with all tumour samples (56%, 18/32) 0.025>P>0.01 (chi2 with Yates' correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2 expression is retained after malignant transformation in colonic epithelium and, although it may potentially be a target for antiproliferative therapy, its ubiquitous expression militates against this. hSSTR5 warrants investigation as a tumour suppressor.
生长抑素类似物可能是晚期结直肠癌全身治疗中有用的新型药物,因为生长抑素可抑制多种细胞类型的增殖。在此,我们报告了32对恶性和正常结肠上皮中生长抑素受体mRNA的表达谱。通过逆转录聚合酶链反应(RT-PCR)和原位杂交在近90%的恶性和正常组织中检测到受体亚型2(hSSTR2)mRNA。在46%的肿瘤样本和45%的黏膜样本中检测到亚型5(hSSTR5)mRNA,但在75%(9/12)的早期肿瘤(管状绒毛状腺瘤、Dukes A和B期)中检测到,而在晚期肿瘤(Dukes C和D期肿瘤)中为31%(5/16),0.05 > P > 0.025(经Yates校正的卡方检验)。与所有肿瘤样本(56%,18/32)相比,转移瘤样本中hSSTR5的表达也降低(11%,1/9),0.025 > P > 0.01(经Yates校正的卡方检验)。其他hSSTRs(1、3和4)表达较少。因此,hSSTR2在结肠上皮恶性转化后仍保留表达,尽管它可能是抗增殖治疗的潜在靶点,但其普遍存在的表达不利于此。hSSTR5作为一种肿瘤抑制因子值得研究。