Tumor promoter PMA stimulates the synthesis and secretion of mouse pro-urokinase in MSV-transformed 3T3 cells: this is mediated by an increase in urokinase mRNA content.

Belin, Dominique; Godeau, François; Vassalli, Jean‐Dominique

doi:10.1002/j.1460-2075.1984.tb02065.x

Cited by 58 publications

(31 citation statements)

References 43 publications

(46 reference statements)

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“…The expression of uPA has been shown to be correlated with many cancers. In addition, TPA treatments have been shown to increase uPA levels in cell lines and mouse skin [6,13,14]. Moreover, we have previously shown that TPA induces a uPA dependent 6 integrin cleavage in normal breast cells MCF10A [6].…”

Section: Introductionmentioning

confidence: 84%

“…In this study we wanted to determine the 6p integrin expression in normal mouse skin and skin tumor tissues. Several pieces of evidence indicate that uPA expression is induced after TPA treatments in different cell lines and on mouse skin [6,[13][14][15]. In addition, MNNG treatment has been shown to induce uPA expression in different cell lines [15,20,21].…”

Section: Discussionmentioning

confidence: 99%

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Integrin A6 Cleavage in Mouse Skin Tumors

Demetriou

Kwei²,

Powell³

et al. 2008

TOCJ

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Abstract:We have previously identified a structural variant of the 6 integrin (Laminin receptor) called 6p. The 6p variant is a 70 kDa form of the full-length 6 integrin (140 kDa) that remains paired with either the 1 or 4 subunit on the cell surface. 6p is produced by urokinase-type plasminogen activator (uPA), which removes the extracellular -barrel domain while the receptor is on the cell surface. The 6p integrin was present in human prostate cancer tissue but not in normal tissue and the cleavage of the 6 integrin extracellular domain promotes tumor cell invasion and migration on laminin. The objective of the present study was to determine whether the 6p integrin is observed in other models of carcinogenesis. Our results indicate detectable low levels of 6p in normal mouse skin, and comparatively elevated levels in mouse papillomas and squamous cell carcinomas induced by DMBA, TPA and MNNG treatments. Furthermore, we have found that 6p was present at high levels in skin melanomas of transgenic mice that over express activated Ha-ras under the control of the tyrosinase promoter. Finally, subcutaneous injection into athymic nude mice of a malignant mouse keratinocyte derived cell line (6M90) that is 6p negative, results in the development of tumors that contain 6p integrin. The latter results indicate that 6p is induced in vivo suggesting that the tumor microenvironment plays a major role in the production of 6p. Taken together, these data suggest that the cell surface cleavage of the 6 integrin may be a novel mechanism of integrin regulation and might be an important step during skin tissue remodeling and during carcinogenesis.

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Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Integrin A6 Cleavage in Mouse Skin Tumors

Demetriou

Kwei²,

Powell³

et al. 2008

TOCJ

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“…RNA extraction. The RNA from early passages of control and DMSO-treated HEp-3 cells was extracted as described previously (1). Briefly, the cells were scraped, pelleted, suspended in buffer, and lysed by Nonidet P-40.…”

Section: Dulbecco Modifiedmentioning

confidence: 99%

“…Oocyte injections and measurements of PA in the oocyte extracts were performed exactly as previously described (1,16,29).…”

Section: Dulbecco Modifiedmentioning

confidence: 99%

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Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin.

Ossowski¹,

Belin²

1985

Mol. Cell. Biol.

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Human carcinoma HEp-3 lost its tumorigenic and metastatic potential upon prolonged culture in vitro. This change was accompanied by a reduced production of plasminogen activator (PA) of the urokinase type (uPA), which is secreted by HEp-3 cells, a change in response to effectors that modulate uPA production, and an alteration of cell morphology. Similar but more rapid changes occurred when malignant HEp-3 cells were exposed to dimethyl sulfoxide (DMSO). uPA activity in the culture medium dropped below 50% of the control level within 6 h after the addition of DMSO and became undetectable after 24 h of treatment. This drop in uPA activity was not caused by an increased production of PA inhibitors. The cell-associated uPA decreased to 25 to 30% of the control level within 6 h of DMSO treatment and remained at this level for at least 96 h; the reduced uPA production was partially accounted for by a rapid decrease in the functional and chemical concentration of uPA mRNA. In contrast, the concentrations of most of the abundant mRNA species did not appear to be significantly affected, and cell growth was only slightly inhibited in the presence of DMSO. Malignant HEp-3 cells treated with DMSO responded to cholera toxin with an enhanced production of uPA, and their morphology became indistinguishable from that of nonmalignant HEp-3 cells grown in vitro for prolonged periods of time. All of the above changes were fully and rapidly reversible. The inhibitory effect of DMSO on PA production appears to be specific for uPA of human cell lines.Human epidermoid carcinoma HEp-3 cells, grown and passaged on the chorioallantoic membranes of chicken embryos, form large tumors at the site of inoculation and metastasize extensively into the organs of the embryo (10,33). This malignant potential is retained only during propagation in vivo. After growth in cell culture for periods of several weeks to several months, the malignant potential of HEp-3 tumor-derived cells is gradually lost (34), although it can be reexpressed through prolonged exposure to in vivo conditions (35). Thus, the decline of the malignant potential accompanying continued growth in vitro represents a transition to a reversible phenotypic state, which is influenced by environmental factors (35).One important correlate of malignancy is the ability of tumor cells to produce elevated levels of plasminogen activators (PAs), as demonstrated by the finding of enhanced PA production in virally and chemically transformed fibroblasts (37,43,46), high enzyme levels in experimental and human tumors (5,6,9,14,32,38), and a coordinate modulation of tumor growth and PA production by hormones (4, 25, 28, 32). More directly, the metastasis of HEp-3 tumors is drastically reduced by an antibody which specifically inhibits the urokinase-type PA (uPA) secreted by the tumor cells (36). All of the above evidence strongly suggests that PAs play an important role in the expression of malignancy.The conversion of malignant HEp-3 cells to a nonmalignant state, which takes place during cultur...

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Modulation of urokinase plasminogen activator gene expression during the transition from quiescent to proliferative state in normal mouse cells.

Grimaldi¹,

Fiore²,

Locatelli³

et al. 1986

The EMBO Journal

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We have investigated the regulation of urokinase (u‐PA) mRNA in quiescent mouse fibroblasts and keratinocytes stimulated to divide by the addition of serum or epidermal growth factor (EGF), respectively. Serum stimulation of quiescent fibroblasts (BALB/c 3T3 or Swiss 3T3) results in an early and transient increase of u‐PA mRNA level, which precedes by several hours the onset of DNA synthesis. A similar response is elicited by EGF stimulation of quiescent keratinocytes. The increase of u‐PA mRNA parallels that of c‐myc mRNA, does not require protein synthesis and is at least in part due to increase in template activity of the u‐PA gene. Induction of terminal differentiation of mouse keratinocytes results in a decrease of u‐PA mRNA which parallels the decrease of thymidine incorporation. In conclusion, variation in the level of u‐PA mRNA is seen during G0/G1 transition and correlates with the proliferative state of these normal mouse cells.

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Tumor promoter PMA stimulates the synthesis and secretion of mouse pro-urokinase in MSV-transformed 3T3 cells: this is mediated by an increase in urokinase mRNA content.

Cited by 58 publications

References 43 publications

Integrin A6 Cleavage in Mouse Skin Tumors

Integrin A6 Cleavage in Mouse Skin Tumors

Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin.

Modulation of urokinase plasminogen activator gene expression during the transition from quiescent to proliferative state in normal mouse cells.

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