Listen up bitches and queens (sorry!) cox2 associated with breast cancer in dogs,cats

[Lani]

and in dogs with her2+ breast cancer

ABSTRACT: COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic fmolecular markers [Breast Cancer Research and Treatment]
Cyclooxygenase (COX)-2 is an inducible enzyme linked to tumor growth and angiogenesis. Its expression occurs in a wide range of preneoplastic and neoplastic conditions in humans, including colon and breast carcinomas. We evaluated the role of COX-2 as a mediator of angiogenesis in feline and canine invasive carcinomas (IMCs) and its role as a prognostic indicator. COX-2 expression was assessed in neoplastic samples and healthy mammary glands by immunohistochemistry, and related to the following clinicopathological parameters: age, tumor size, histologic type, tumor grading, vessel invasion, estrogen (ER) and progesterone receptor (PR) status, Ki-67, HER-2 overexpression, microvessel density (MVD), VEGF expression and overall survival (OS). In both species, COX-2 immunoreactivity was not observed in healthy tissues, whereas 96% of feline and 100% of canine invasive carcinomas scored positive. In queens, COX-2 overexpression was significantly correlated to ER-negative status (p=0.04) and to increased PR (p=0.038) expression, and angiogenesis assessed by VEGF expression (p=0.002). In bitches an increased COX-2 expression was significantly correlated to HER-2 overexpression (p=0.013) and to tumor dedifferentiation (p=0.03). In both species increased levels of COX-2 were correlated to poorer prognosis (p=0.03 in dogs and p=0.002 in cats). COX-2 is expressed in mammary tissues during tumorigenesis and its expression is associated with a poorer prognosis in bitches and queens. The correlation of COX-2 expression and angiogenesis provides support for a potential role of COX-2 inhibitors for the prevention and the treatment of feline IMCs via their anti-angiogenic properties. In the canine species, moreover, COX-2 may be important for mediating HER-2 induced mammary tumors.

[R.B.]

This very informative article seems to be saying the same thing in a more technical and indierct way.

http://edrv.endojournals.org/cgi/content/full/26/3/331

When I saw the straight line graph between CPY19 the gene encoding aromatase and cox a light went on.

Aromatase is the oestrogen percusor.

The article has a good schematic and some interesting thoughts on flavanoids etc as aromatase inhibitors.

And what is COX 1 and 2 made from omega six. Excess six in cell membranes causal to dietary intake must equal greater expression at call out via PGE 2 etc.


RB


ABSTRACT

http://edrv.endojournals.org/cgi/con...ll/26/3/331/F4

B. Aromatase gene expression
Over the past two decades, knowledge of the biochemistry, molecular biology, and regulation of aromatase has increased greatly. The aromatase gene, designated CYP19, encodes the cytochrome P450arom, and this gene is located on chromosome 15q21.1. The coding region is approximately 30 kb in size, and the regulatory region is approximately 93 kb (9, 15). The aromatase gene consists of 10 exons, and its full-length cDNA of 3.4 kb encodes for a protein of 503 amino acids. The aromatase protein is a glycosylated cytochrome P450 protein with a molecular mass of approximately 58,000 Da (16). The regulation of aromatase is complex in various tissues, and several tissue-specific promoter regions have been identified upstream from the CYP19 gene (9, 17, 18)...................

The increased expression of aromatase cytochrome P450arom observed in breast cancer tissues is associated with a switch in the major promoter region used in gene expression, with promoter PII being the predominant promoter used in breast cancer tissues (24). As a result of the use of the alternate promoter, the regulation of estrogen biosynthesis switches from one controlled primarily by glucocorticoids and cytokines to a promoter regulated through cAMP-mediated pathways (24). Prostaglandin E2 (PGE2) increases intracellular cAMP levels and stimulates estrogen biosynthesis (24), whereas other autocrine factors such as IL-1ß do not appear to act via PGE2 (25).

Local production of PGE2 via the cyclooxygenase isozymes (constitutive COX-1 isozyme and inducible COX-2 isozyme) can influence estrogen biosynthesis and estrogen-dependent breast cancer. This biochemical mechanism may explain epidemiological observations of the beneficial effects of nonsteroidal antiinflammatory drugs (NSAIDs) on breast cancer (26, 27, 28, 29). Investigations using human breast cancer patient specimens demonstrated a strong linear correlation between CYP19 expression and the sum of COX-1 and COX-2 expression (30). Gene expression analysis for CYP19, COX-1, and COX-2 were performed in 20 human breast cancer specimens and in five normal control breast tissue samples. A positive correlation was observed between CYP19 expression and the greater extent of breast cancer cellularity (Fig. 4AGo), in agreement with literature reports showing that aromatase levels were higher in tumors than in normal tissue. Furthermore, a positive linear correlation was observed between COX-2 expression breast cancer cellularity in each sample. Linear regression analysis using a bivariate model shows a strong linear association between CYP19 expression and the sum of COX-1 and COX-2 expression (Fig. 4BGo). Similar correlations between CYP19 expression and COX-2 expression in breast cancer patient specimens have been confirmed in other laboratories (31).

[R.B.]

This very informative article seems to be saying the same thing in a more technical and indierct way.

http://edrv.endojournals.org/cgi/content/full/26/3/331

When I saw the straight line graph between CPY19 the gene encoding aromatase and cox a ligth went on.

Aromatase is the oestrogen percusor.

The article has a good schematic and some interesting thoughts on flavanoids etc as aromatase inhibitors.

And what is COX 1 and 2 made from omega six. Excess six in cell membranes causal to dietary intake must equal greater expression at call out via PGE 2 etc.


RB






B. Aromatase gene expression
Over the past two decades, knowledge of the biochemistry, molecular biology, and regulation of aromatase has increased greatly. The aromatase gene, designated CYP19, encodes the cytochrome ..................

The increased expression of aromatase cytochrome P450arom observed in breast cancer tissues is associated with a switch in the major promoter region used in gene expression, with promoter PII being the predominant promoter used in breast cancer tissues (24). As a result of the use of the alternate promoter, the regulation of estrogen biosynthesis switches from one controlled primarily by glucocorticoids and cytokines to a promoter regulated through cAMP-mediated pathways (24). Prostaglandin E2 (PGE2) increases intracellular cAMP levels and stimulates estrogen biosynthesis (24), whereas other autocrine factors such as IL-1ß do not appear to act via PGE2 (25).

Local production of PGE2 via the cyclooxygenase isozymes (constitutive COX-1 isozyme and inducible COX-2 isozyme) can influence estrogen biosynthesis and estrogen-dependent breast cancer. This biochemical mechanism may explain epidemiological observations of the beneficial effects of nonsteroidal antiinflammatory drugs (NSAIDs) on breast cancer (26, 27, 28, 29). Investigations using human breast cancer patient specimens demonstrated a strong linear correlation between CYP19 expression and the sum of COX-1 and COX-2 expression (30). Gene expression analysis for CYP19, COX-1, and COX-2 were performed in 20 human breast cancer specimens and in five normal control breast tissue samples. A positive correlation was observed between CYP19 expression and the greater extent of breast cancer cellularity (Fig. 4AGo), in agreement with literature reports showing that aromatase levels were higher in tumors than in normal tissue. Furthermore, a positive linear correlation was observed between COX-2 expression breast cancer cellularity in each sample. Linear regression analysis using a bivariate model shows a strong linear association between CYP19 expression and the sum of COX-1 and COX-2 expression (Fig. 4BGo). Similar correlations between CYP19 expression and COX-2 expression in breast cancer patient specimens have been confirmed in other laboratories (31).



P450arom,http://edrv.endojournals.org/cgi/con...ll/26/3/331/F4

[Lani]

it is one of three ENZYMES utilized to convert other hormones/precursors (DHEA, testosterone, etc) into estrogen and these hormones/precursors are particularly important in post-menopausal women where they are the primary source of estrogen. More pertinently breast cancer cells seem to make their own estrogen and these three enzymes seem to be intimately involved in that. AIs seem to inhibit aromatase (there are several generations of these and some are steroidal and some nonsteroidal), tibolone seems to inhibit one or two of the others. It is all FAR FROM COMPLETELY UNDERSTOOD and news of more intricacies regarding this emerge all the time.

NSAIDs seem to have aromatase inhibitor properties as well as antiangiogenic properties and it seems cox2 is UP TO NO GOOD IN MANY WAYS in breast cancer.

Hope this helps