Differential expression of prostaglandin h synthase isozymes during multistage carcinogenesis in mouse epidermis

Müller‐Decker, Karin; Scholz, K.; Marks, Friedrich; Fürstenberger, Gerhard

doi:10.1002/mc.2940120106

Cited by 140 publications

(110 citation statements)

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“…34,35 COX-2 seems to be involved in manifestations of infectious and neoplasmatic diseases. [36][37][38] In this study, we found that COX-1 mRNA continuously and extensively increased during experimental period, while COX-2 mRNA initially decreased and transiently increased. The results suggest that the increased COX-1 has the primary role on hyperplasia of intestinal epithelium through PGE 2 production in VMH-lesioned rats.…”

Section: Vmh Lesions In Jejunal Hyperplasiamentioning

confidence: 87%

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase

Kageyama

Endo

et al. 2003

Int J Obes

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BACKGROUND:We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve. OBJECTIVE: To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats. DESIGN: At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2 0 -deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)-a mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting. RESULTS: Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF-a mRNA were unchanged in VMH lesioned rats. CONCLUSION: VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E 2 , induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.

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Section: Vmh Lesions In Jejunal Hyperplasiamentioning

confidence: 87%

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase

Kageyama

Endo

et al. 2003

Int J Obes

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“…COX-2, in contrast to the constitutively expressed COX-1 which contributes to physiological functions in most tissues, is inducible and has proven involvement in inflammatory responses and cell proliferation (Herschman, 1994). It is known that COX-2 is highly expressed in colon, stomach, skin and mammary tumours (Kargman et al, 1995;Müller-Decker et al, 1995;DuBois et al, 1996;Liu et al, 1996;Ristimäki et al, 1997), in conjunction with increased levels of prostaglandins (Lupulescu, 1996).…”

Section: Discussionmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

et al. 2000

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Summary Inclusion of phenacetin among 'proven' human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case-control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non-or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection.

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“…COX-2 expression has been shown to be increased in rodent skin papillomas and carcinomas promoted by TPA, and rodent skin tumorigenesis can be inhibited by NSAIDS (7). Thus, the ability of thapsigargin and okadaic acid to induce COX-2 expression could be relevant to their tumor promoting activity.…”

Section: Figmentioning

confidence: 99%

“…COX-2 is an immediate-early gene inducible by cytokines, growth factors, and the tumor promoter 12-tetradecanoylphorbol-13-myristate (TPA) (2)(3)(4)(5). COX-2 expression and prostaglandin E 2 (PGE 2 ) levels are increased in colon (1,6) and skin (7) tumors, and non-steroidal anti-inflammatory drugs (NSAIDS) inhibit carcinogenesis in several systems (1,(7)(8). Transformation of epithelial cells with the ras or src oncogenes causes elevated COX-2 expression and increased PGE 2 synthesis (9).…”

mentioning

confidence: 99%

“…Previous observations suggest that COX-2 might be regulated by thapsigargin, a Ca 2ϩ -ATPase inhibitor, and okadaic acid, a phosphatase inhibitor, which are both potent skin tumor promoters in rodents. COX-2 expression is increased in skin tumors promoted by TPA, and skin tumorigenesis can be inhibited by NSAIDS (7). Furthermore, both thapsigargin and okadaic acid cause increased prostaglandin synthesis in vitro (12)(13)(14)(15).…”

mentioning

confidence: 99%

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Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

Ledwith¹,

Pauley²,

Wagner³

et al. 1997

Journal of Biological Chemistry

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Increased expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin synthesis, has been associated with growth regulation and carcinogenesis in several systems. COX-2 is known to be induced by cytokines and the skin tumor promoter 12-tetradecanoylphorbol-13-myristate (TPA). In the present study, we investigated the effects of several non-TPA-type tumor promoters on COX-2 expression in immortalized mouse liver cells. Specifically, we tested peroxisome proliferators (PPs), which are rodent liver tumor promoters that cause gross alterations in cellular lipid metabolism, the rodent liver tumor promoter phenobarbital, and the skin tumor promoters okadaic acid and thapsigargin. The PPs Wy-14643, mono-ethylhexyl phthalate, clofibrate, ciprofibrate ethyl ester, and eicosatetraynoic acid each caused large increases in COX-2 mRNA and protein, with maximal expression seen approximately 10 h after treatment of quiescent cells. COX-2 expression was also induced by thapsigargin, okadaic acid, and calcium ionophore A23187, but not by phenobarbital or the steroid PP dehydroepiandrosterone sulfate. Induction of COX-2 expression generally resulted in increased synthesis of prostaglandin E 2 (PGE 2 ). However, the PPs caused little or no increase in PGE 2 levels, and they inhibited serum-induced PGE 2 synthesis. Unlike nonsteroidal anti-inflammatory drugs, the PPs do not directly inhibit cyclooxygenase enzyme activity in vitro. Thus, PPs regulate prostaglandin metabolism via both positive (COX-2 induction) and inhibitory mechanisms. In summary, the strong induction of COX-2 expression by PPs, thapsigargin, and okadaic acid suggests a possible role for COX-2 in the growth regulatory activity of these non-TPA-type tumor promoters.

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Differential expression of prostaglandin h synthase isozymes during multistage carcinogenesis in mouse epidermis

Cited by 140 publications

References 53 publications

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase

Non-steroidal anti-inflammatory drugs and bladder cancer prevention

Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells

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