Mechanisms for the Prevention of Gastrointestinal Cancer: The Role of Prostaglandin E&lt;sub&gt;2&lt;/sub&gt;

Backlund, Michael G.; Mann, Jason R.; DuBois, Raymond N.

doi:10.1159/000086629

Cited by 95 publications

(83 citation statements)

References 43 publications

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“…colon (91), and gastrointestinal (92,93) cancers. Decreased expression of this protein, which has tumor suppressor activity in colorectal cancer (92,93), is accompanied by increased expression of COX-2, a PG-synthesizing enzyme and a 15-PGDH physiological antagonist that has been implicated in tumor progression in various malignancies (94 -99). Recently Muller-Decker et al (100) reported that overexpression of COX-2 in keratin 5-positive cells of the mouse mammary gland caused an increase in PGE 2 , cystic duct dilations, adenosis, and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Apocrine Cysts of the Breast

Celis

Gromov

Moreira

et al. 2006

Molecular & Cellular Proteomics

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Up to one-third of women aged 30 -50 years have cysts in their breasts and are presumed to be at increased risk of developing breast cancer. Here we present an extensive proteomic and immunohistochemistry (IHC) study of breast apocrine cystic lesions aimed at generating specific biomarkers and elucidating the relationship, if existent, of apocrine cysts with cancer phenotype. To this end we compared the expression profiles of apocrine macrocysts obtained from mastectomies from high risk cancer patients with those of cancerous and non-malignant mammary tissue biopsies collected from the same patients. We identified two biomarkers, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase, that were expressed specifically by apocrine type I cysts as well as by apocrine metaplastic cells in type II microcysts, terminal ducts, and intraductal papillary lesions. No expression of these markers was observed in non-malignant terminal ductal lobular units, type II flat cysts, stroma cells, or fat tissue as judged by IHC analysis of matched non-malignant tissue samples collected from 93 high risk patients enrolled in our cancer program. IHC analysis of the corresponding 93 primary tumors indicated that most apocrine changes have little intrinsic malignant potential, although some may progress to invasive apocrine cancer. None of the apocrine lesions examined, however, seemed to be a precursor of invasive ductal carcinomas, which accounted for 81% of the tumors analyzed. Our studies also provided some insight into the origin, development, and enlargement of apocrine cysts in mammary tissue. The successful identification of differentially expressed proteins that characterize specific steps in the progression from early benign lesions to apocrine cancer opens a window of opportunity for designing and testing new approaches for pharmacological intervention, not only in a therapeutic setting but also for chemoprevention, to inhibit cyst development as both 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies. Molecular & Cellular Proteomics 5:462-483, 2006.The human breast presents many benign lesions that involve both the glandular and stromal tissues. These include fibrocystic changes, benign breast tumors, and breast inflammatory disease (1). Fibrocystic changes affect more than 50% of women during their lifetime and are comprised of cystic dilation of ducts, apocrine metaplasia of ductal epithelium, fibrosis, adenosis, and intraductal epithelial proliferation (Ref. and references therein).Cysts are fluid-filled sacs that usually develop in the upper half of the breast and are most common in women between 30 and 50 years of age (3). They are also found in menopausal women on hormone replacement therapy. Cysts start as a microscopic dilation of the ductules (microcyst) but can enlarge and reach sizes of a couple of centimeters in diameter (macrocysts) causing pain and discomfort due to the tens...

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Section: Discussionmentioning

confidence: 99%

Apocrine Cysts of the Breast

Celis

Gromov

Moreira

et al. 2006

Molecular & Cellular Proteomics

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“…Since AA is the precursor of PGE2, this may contribute to the high prevalence of colon cancer in the Western world [9] . In contrast, diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are mainly found in fish oil, might reduce the risk of colon cancer development, and an inverse association of consumption of fish and colon cancer has been observed epidemiologically [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

Habbel¹,

Weylandt²,

Lichopoj³

et al. 2009

WJG

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AIM:To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth. METHODS:The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2-ELISA.RESULTS: AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time-and dosedependent manner. Furthermore, DHA down-regulated mRNA of bcl-2 and up-regulated p21. Interestingly, DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner. CONCLUSION:These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

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“…These include arthritis (Honda et al, 2006), fever, chronic pain (Mabuchi et al, 2004), sepsis, burn injury (Hahn & Gamelli, 2000), inflammatory bowel disease (Subbaramaiah et al, 2004), and carcinogenic processes in colorectal cancer (Backlund et al, 2005). In the treatment of inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used, and are effective in the management of pain, fever, redness and edema arising as a consequence of inflammatory mediator release (Ferreira, 2002).…”

Section: Introductionmentioning

confidence: 99%