McArdle L, Rafferty M, Maelandsmo G M, Bergin O, Farr C J, Dervan P A, O'Loughlin S, Herlyn M, Easty D J
Department of Pathology, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
J Invest Dermatol. 2001 Nov;117(5):1255-60. doi: 10.1046/j.0022-202x.2001.01534.x.
Phospho-tyrosine levels are increased in melanoma, apparently consistent with reports of elevated protein tyrosine kinase activity. Some protein tyrosine kinases are encoded by oncogenes and have been implicated in melanoma genesis. Decreased protein tyrosine phosphatase activity may also increase phospho-tyrosine. Protein tyrosine phosphatase genes are candidate tumor suppressors and loss of expression may contribute to melanoma genesis. Here we survey protein tyrosine phosphatase expression in pigment cells. Protein tyrosine phosphatase genes were cloned by reverse transcriptase polymerase chain reaction using degenerate primers based upon conserved sequences within the phosphatase catalytic domain. Reaction products were cloned and sequenced: 118 and 113 partial protein tyrosine phosphatase products were isolated from normal melanocytes and melanoma cells, respectively. Northern blotting analysis was used to study expression of 15 protein tyrosine phosphatase genes. Expression of PTP-kappa and PTP-pi was absent or downregulated in more than 20% of melanoma cell lines and in some unmanipulated melanoma biopsies. These closely related enzymes are members of the 2B receptor protein tyrosine phosphatase family previously implicated in contact inhibition. Loss of protein tyrosine phosphatase expression may contribute to the abnormal tyrosine phosphorylation seen in melanoma; these genes are candidate tumor suppressors.
黑色素瘤中磷酸化酪氨酸水平升高，这显然与蛋白酪氨酸激酶活性升高的报道一致。一些蛋白酪氨酸激酶由癌基因编码，并与黑色素瘤的发生有关。蛋白酪氨酸磷酸酶活性降低也可能导致磷酸化酪氨酸增加。蛋白酪氨酸磷酸酶基因是候选肿瘤抑制基因，其表达缺失可能促成黑色素瘤的发生。在此，我们研究色素细胞中蛋白酪氨酸磷酸酶的表达情况。基于磷酸酶催化结构域内的保守序列，使用简并引物通过逆转录聚合酶链反应克隆蛋白酪氨酸磷酸酶基因。对反应产物进行克隆和测序：分别从正常黑素细胞和黑色素瘤细胞中分离出118个和113个部分蛋白酪氨酸磷酸酶产物。采用Northern印迹分析研究15个蛋白酪氨酸磷酸酶基因的表达。在超过20%的黑色素瘤细胞系以及一些未经处理的黑色素瘤活检组织中，PTP-κ和PTP-π的表达缺失或下调。这些密切相关的酶是先前与接触抑制有关的2B受体蛋白酪氨酸磷酸酶家族的成员。蛋白酪氨酸磷酸酶表达缺失可能导致黑色素瘤中出现异常的酪氨酸磷酸化；这些基因是候选肿瘤抑制基因。
