cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis

Kadomatsu, Kenji; Tomomura, Mineko; Muramatsu, Takashi

doi:10.1016/s0006-291x(88)80505-9

Cited by 454 publications

(299 citation statements)

References 15 publications

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“…It is a product of a retinoic acidresponsive gene. Midkine and pleiotrophin (PTN) compose the heparin-binding growth-associated molecule family, which is distinct from other heparin-binding growth factor families (Kadomatsu et al, 1988;Tomomura et al, 1990). Midkine and PTN also lack similarity to other growth factors or cytokines (Salama et al, 2006).…”

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Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P ¼ 0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P ¼ 0.0073). Multivariate analysis revealed that MK expression was an independent prognostic factor (P ¼ 0.0033). This is the first report of an association between MK expression and pancreatic head carcinoma. Midkine may play an important role in the progression of pancreatic head carcinoma, and evaluation of MK expression is useful for predicting malignant properties of pancreatic head carcinoma.

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confidence: 99%

Clinical significance of midkine expression in pancreatic head carcinoma

et al. 2007

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“…Midkine (MK), originally isolated as a product of a retinoic acid-responsive gene in an embryonal carcinoma cell differentiation system, is a heparin-binding growth factor (Kadomatsu et al, 1988;Tomomura et al, 1990 a,b) implicated in neuronal survival and differentiation (Muramatsu and Muramatsu, 1991;Michikawa et al, 1993;Unoki et al, 1994), carcinogenesis (Tsutsui et al, 1993;Nakagawara et al, 1995), fibrinolysis (Kojima et al, 1995), wound healing (Yoshida et al, 1995) and development (Kadomatsu et al, 1990;Mitsiadis et al, 1995a, b). MK belongs to a novel growth factor family whose only members so far are MK and pleiotrophin (PTN)/HB-GAM (Muramatsu, 1993(Muramatsu, , 1994.…”

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Midkine induces the transformation of NIH3T3 cells

Kadomatsu

Hagihara²,

Akhter³

et al. 1997

Br J Cancer

138

111

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Summary Midkine (MK) is a heparin-binding growth factor and is frequently expressed at high levels in many human carcinomas. To investigate further the roles of MK in the regulation of cell growth, we introduced MK expression in NIH3T3 cells. A mixture of transfectants of an MK expression vector, but not a control vector, formed colonies in soft agar, showed an elevated cell number at confluence, and formed tumours in nude mice. An interesting characteristic of the transformed cells was that they became spontaneously detached from the culture dish substratum. In the transformed cells, MK was not only secreted, but also localized, in the perinuclear region as spots. The present data indicate that MK has the potential to transform NIH3T3 cells and suggest that overexpression of the MK gene may promote unregulated cell growth in vivo.

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“…In thyroid papillary carcinomas, it has been suggested that transforming growth factor alpha and epidermal-growth-factor receptor are involved in an autocrine loop (24). Considered in connection with the fact that MK is a member of a novel family of heparin-binding growth factors (1)(2)(3), the aberrant MK expression in thyroid papillary carcinomas might reflect the amplification of autocrine activity.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and In Situ Hybridization Analyses of Midkine Expression in Thyroid Papillary Carcinoma

et al. 2000

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Midkine (MK) is a novel heparin-binding growth factor whose gene has been identified in embryonal carcinoma cells in early stages of retinoic acidinduced differentiation. We immunohistochemically examined 90 thyroid papillary carcinomas (85 invasive type and five encapsulated type), using a rat IgG2a monoclonal antibody against the carboxyl terminal region of human MK in archival paraffin sections. The thyroid tumors exhibited an intense reaction in the cytoplasm. Most of the papillary carcinomas (77/90), had tumor cells that expressed MK. These were classified into the following two types: invasive type (76/85) and encapsulated type (1/5). Notably, the intensity of MK was stronger at the invading border area of the tumors than in the center. In tissues adjacent to the cancer tissues, normal follicular epithelial cells expressed MK very faintly or not at all. The in situ hybridization analysis revealed that the signals of MK transcripts were found in the cytoplasm of the cancer cells. In the noncancerous follicular epithelial cells adjacent to neoplasm the signals of MK transcripts were detected very weakly or not at all. The distribution and localization of the MK-transcript signals determined by in situ hybridization analysis were similar to those obtained by immunohistochemical analysis. We conclude that thyroid papillary carcinoma strongly expresses MK protein and messenger RNA, and that this overexpression may relate to the development and invasion of these carcinomas.

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cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis

Cited by 454 publications

References 15 publications

Clinical significance of midkine expression in pancreatic head carcinoma

Clinical significance of midkine expression in pancreatic head carcinoma

Midkine induces the transformation of NIH3T3 cells

Immunohistochemical and In Situ Hybridization Analyses of Midkine Expression in Thyroid Papillary Carcinoma

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