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Abstract：
Rhabdomyosarcomas of the parotid and submandibular glands have the histological appearance of a skeletal muscle tumor yet can be found in tissue with no striated muscular elements. We examine the potential cell-of-origin for rhabdomyosarcoma and whether salivary tumors represent primary malignancy or metastasis. We have previously established genetically engineered mouse models of rhabdomyosarcoma. In these mice, rhabdomyosarcoma is only induced when a Pax3:Foxo1 fusion oncogene is activated with concurrent loss of p53 function (for alveolar rhabdomyosarcoma) or loss of p53 function alone (for embryonal rhabdomyosarcoma) using Cre-lox technology. These mutations are only activated under the control of promoters specific for selected cell lineages, previously thought to be myogenesis-restricted. RT-PCR and immunohistochemistry for lineage-specific promoter gene products reveal these promoters are active in wild-type mouse salivary gland. Given that mouse rhabdomyosarcoma frequently originates in the salivary glands and these myogenic-related promoters are normally expressed in salivary tissue, a high likelihood exists that the salivary gland contains a cell-of-origin of this muscle-related cancer.
摘要：
腮腺和颌下腺的横纹肌肉瘤具有骨骼肌肿瘤的组织学外观，但可以在没有横纹肌成分的组织中发现。我们检查了横纹肌肉瘤的潜在起源细胞，以及唾液肿瘤是否代表原发性恶性肿瘤或转移。我们以前已经建立了横纹肌肉瘤的基因工程小鼠模型。在这些老鼠身上,只有当使用Cre-lox技术激活Pax3：Foxo1融合癌基因并同时丧失p53功能（对于肺泡横纹肌肉瘤）或单独丧失p53功能（对于胚胎性横纹肌肉瘤）时，才会诱发横纹肌肉瘤。这些突变仅在特定于选定细胞谱系的启动子的控制下被激活。以前被认为是肌生成受限的。谱系特异性启动子基因产物的RT-PCR和免疫组织化学显示这些启动子在野生型小鼠唾液腺中具有活性。鉴于小鼠横纹肌肉瘤通常起源于唾液腺，并且这些肌源性相关启动子通常在唾液组织中表达，唾液腺很可能含有这种肌肉相关癌症的起源细胞。
