PTGS2:
The very existence of the amplification of this gene attests to the fact that in Esophageal cancer the stress imposed by chemical and traumatic irritants will involve inflammatory pathways and over-expression of Cyclins and growth Factors. Over-expression of COX-2 that this gene amplification represents leads to the formation of prostaglandins which decrease membrane protection by PGH2 and PGI2, with ulceration at the tumor level resulting. When you see an ulcerated cancer in the stomach or at the base of the Esophagus, you understand what happened!
It points to the potential importance of Interferon treatment as an adjunct therapy.
MSR1 (Macrophage Scavanger Receptor 1):
This gene amplification may stop Macrophages from removing irritated and altered cancer cells,. Irritated neoplastic cells often contain HSP (Heat shock proteins) altered proteins that should trigger action by the scavenger. But Mutation at MRS1 leads to a tolerance of the existence of these neoplastic cells. The HSP are normally generated by HSPA1A, a gene " located in the major histocompatibility complex class III
region, in a cluster with two closely related genes which encode similar
proteins."(wikipedia)
In a normal cell, HSP will interact with ASK1 (Apoptosis Signal-Regulating Kinase1) and trigger independently Apoptosis, or use the same molecule as MAP3K5 to stimulate c-JUN (the stress pathway). And don't tell me we didn't warn you that, in the pathogenesis of Esophageal cancers, irritants will stimulate C-JUN the stress related family member of the MAP Kinases. ASK1 interacts with TNF alpha Receptor and a bunch of DNA protein Kinases that will lead to the production of inflammatory factors including the Autoimmune Antigen Ku!
There you have it, do not be surprised that HSP has much to do with other altered proteins called Amyloids...and you start getting the right idea that Alzheimer's disease is around the corner! Yes, the tolerance induced by Mutated MSR1 and HSP has something to do with the disposition of Amyloid deposits!
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