cox 2 contributes to her2+ breast cancer and tumorigenesis in mice

[Lani]

ABSTRACT: HER2/neu-Induced Mammary Tumorigenesis and Angiogenesis Are Reduced in Cyclooxygenase-2 Knockout Mice [Cancer Research; Subscribe]
The inducible prostaglandin synthase cyclooxygenase-2 (Cox-2) is overexpressed in ~40% of human breast cancers and at higher frequencies in preinvasive ductal carcinoma in situ (DCIS). Cox-2 expression is particularly associated with overexpression of human epidermal growth factor receptor 2 (HER2/neu). To definitively interrogate the role of Cox-2 in mammary neoplasia, we have used a genetic approach, crossing Cox-2-deficient mice with a HER2/neu transgenic strain, MMTV/NDL. At 20 weeks of age, mammary glands from virgin MMTV/NDL females contained multiple focal tumors, or mammary intraepithelial neoplasias, which histologically resembled human DCIS. Mammary tumor multiplicity and prostaglandin E2 (PGE2) levels were significantly decreased in Cox-2 heterozygous and knockout animals relative to Cox-2 wild-type controls. Notably, the proportion of larger tumors was decreased in Cox-2-deficient mice. HER2/neu-induced mammary hyperplasia was also substantially reduced in Cox-2 null mice. Additionally, mammary glands from Cox-2 knockout mice exhibited a striking reduction in vascularization, and expression of proangiogenic genes was correspondingly reduced. Decreased vascularization was observed both in dysplastic and normal-appearing regions of Cox-2-null mammary glands. Our data provide the first genetic evidence that Cox-2 contributes to HER2/neu-induced mammary tumorigenesis. This finding may help to explain the reduced risk of breast cancer associated with regular use of nonsteroidal anti-inflammatory drugs.

[Unregistered]

If this was of interest I strongly suggest you read the post on the importance of omega three and six to breast cancer on the articles of interest section.

Omega six is a percusor of cox 2s. The balance between omega 3 and six has gone from a historic level of around 1:1 to an average of one to ten and up.

RB

[saleboat]

I've heard that Celebrex (a Cox-2 inhibitor) is being studied for its anti-cancer properties. Has anyone here heard of that? I think it has shown some efficiacy in colon cancer, but is still investigational in breast cancer.

Jen

[Becky]

Aspirin is a Cox 1 and a Cox 2 inhibitor. Because of its Cox 1 status, the Cox 2 inhibition does not cause the heart problems that the Vioxx, Celebrex do.

Celebrex was being studied in breast cancer and it was that study that the heart problems were apparent and started bringing this problem with the Cox 2 inhibitors to light. That study was halted.

Take an aspirin, its good for you for a whole host of reasons - unless you get stomach upset from it or gastric bleeding (which some people do). I take one 81mg every day. I don't know if this is enough but it is to prevent stroke in women and heart attacks in men (helps women on the heart attack front after age 65).

Zyflamend is a herb mixture (with rosemary which has known Cox 2 inhibition properties) that has Cox 2 inhibition properties. You can google it and read on many supplement sites its virtues but an aspirin is cheaper and has known properties and quality control.

Best regards

Becky