Adrenomedullin Suppresses Mitogenesis in Rat Mesangial Cells via cAMP Pathway

Chini, Eduardo N.; Choi, Eunhee; Grande, Joseph P.; Burnett, John C.; Douša, Thomas P.

doi:10.1006/bbrc.1995.2544

Cited by 143 publications

(98 citation statements)

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“…AM stimulates growth in osteoblasts (Cornish et al, 1997), oral keratinocytes (Kapas et al, 1997), adrenal cells (Andreis et al, 2000), retinal pigment epithelial cells (Udono et al, 2000) and teratocarcinoma cells (Moody et al, 2000), and suppresses growth in cardiac fibroblasts (Tsuruda et al, 1999), mesangial (Chini et al, 1995) and neuroblastoma (Ando et al, 1997) cells. Interestingly, both proliferative (Iwasaki et al, 1998) and antiproliferative (Kano et al, 1996) actions have been reported for AM in smooth muscle cells, depending on the culture conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, AM has been reported to act as a cell growth regulator . It stimulates the growth in some types of cells (Andreis et al, 2000;Cornish et al, 1997;Kapas et al, 1997;Moody et al, 2000;Udono et al, 2000), but suppresses cell growth in others (Ando et al, 1997;Chini et al, 1995;Tsuruda et al, 1999). AM and its receptors are expressed during fetal development, in a variety of tumors, and in several cancer cell lines, suggesting an autocrine/paracrine role of this peptide in the control of growth and tumorigenesis (Martinez et al, 1997a,b;Miller et al, 1996;Montuenga et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Abasolo

Yang

Haleem

et al. 2003

Molecular and Cellular Endocrinology

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The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.9599/0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G 1 /G 0 cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms. #

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Abasolo

Yang

Haleem

et al. 2003

Molecular and Cellular Endocrinology

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“…AM has recently been demonstrated to be a mitogen for Swiss 3T3 cells, elevating cAMP in a dose dependent fashion and mediating a protein kinase A response (44). Conversely, AM has also been reported to suppress the growth of rat mesangial cells via the cAMP pathway (45). This diametric relationship of AM and growth regulation in different cell systems appears to be directly involved with the protein kinase pathway and probably relates to RI/RII activity (38).…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin Expression in Human Tumor Cell Lines ITS POTENTIAL ROLE AS AN AUTOCRINE GROWTH FACTOR

Miller

Martı́nez

Unsworth

et al. 1996

Journal of Biological Chemistry

287

201

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Adrenomedullin (AM)1 is a recently identified hypotensive peptide initially isolated from human pheochromocytoma (1). AM and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), are the two known bioactive products generated from post-translational enzymatic processing of the 185-amino acid prepro-AM molecule (1-3). Both AM and PAMP are amidated peptides. However, they have been shown to mediate their vasodilatory effects through distinctly different receptor systems (4). AM stimulates adenyl cyclase activity which elevates cAMP levels in smooth muscle cells. It is structurally related to calcitonin gene-related peptide (CGRP), and its vasodilatory effect is inhibited by the CGRP antagonist, CGRP 8 -37 (5-10). Conversely, PAMP has no amino acid sequence homology to AM or CGRP and its biological effects are not blocked by CGRP 8 -37 suggesting the involvement of a separate receptor system (4). Human AM cDNA has been cloned and mRNA expression identified in the adrenal glands, lung, kidney, and heart (2). A high degree of base sequence homology has been found between AM mRNAs isolated from other mammalian species, including rat and pig (11,12). AM has been also implicated as an important regulator of renal function having natriuretic and diuretic action (13, 14), a potent bronchodilator (15), a regulator of certain central brain actions (16,17), and a suppressor of aldosterone, adrenocorticotropin and insulin release (18 -20). The receptor for AM (AM-R) was recently cloned and sequenced (21); it contains seven transmembrane domains and belongs to the G protein-linked receptor superfamily. Finally, we and others have shown that AM is expressed in a variety of human tumors of both pulmonary and neural lineage including small cell lung cancer, adenocarcinoma, bronchoalveolar carcinoma, squamous cell carcinoma, and lung carcinoids; and ganglioblastoma and neuroblastoma (22,23). In an attempt to further study the distribution of AM and its receptor in human tumors and determine their role in these malignant disorders, we have used molecular, biochemical, and in vitro techniques to analyze a variety of human cancer cell lines of lung, breast, brain, ovary, colon, prostate, and hemopoietic lineages. MATERIALS AND METHODS Cell Lines and NormalTissue-Tumor cell lines evaluated in this study were as follows: small cell lung carcinomas (SCLC, H60, H69c, H82, H146, H187, H209, H345, H446, N417, H510, N592, H735, H774, H889, H1092), non-small cell lung carcinomas (NSCLC, H23, H157, H460, H676, H720, H727, H820, H1264, H1385, H1404, H2087, H2228, A549, UMC11), breast (SK-BR-3, ZR75-1, MCF-7, BT-20, MDA-MD231, BT-474, H2380), colon (H630, SNUC-1), nervous system (T98G (glioblastoma), TC106, CHP100, TC17, PNET, Peii, SY5Y, AS, LAN-1, KCNR-C, KCNR-DRA (neuroblastomas of the peripheral nervous system)), ovarian (NIH:OVCAR-3, SKOV3, OVT2, A2780, CP70), prostate (DU-145), adrenal (H295), chondrosarcoma (SW578), and chronic monocytic leukemia (U937). Additional NSCLC cell lines used to evaluate AM-R that are not ...

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“…Several studies have now shown that AM can function as a growth regulator in both normal and malignant cells (Chini et al 1995, Kano et al 1996, Withers et al 1996. In vitro  4.…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin expression in the mouse mammary gland: evidence for the mature form in milk

Jahnke¹,

Miller²,

Martı́nez³

et al. 1997

Journal of Molecular Endocrinology

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Adrenomedullin (AM) is a recently identified amidated peptide produced by a variety of tissue types. We have investigated the involvement of AM and its receptor (AM-R) in developing mouse mammary glands and have examined what influence ovarian hormones have on AM and AM-R expression in this system. Tissues from ductal morphogenesis, virgin adult, pregnancy, and lactation stages were assessed for AM and AM-R by molecular, biochemical and immunohistochemical techniques. Results from these studies indicated that messenger RNA for AM and AM-R and immunoreactivity for AM were expressed in the luminal epithelium of small and large ducts and in terminal end buds. Immunoreactive AM was identified as a cytoplasm component of ductal cells, with some cells also having nuclear staining. Western blot analysis of mammary gland tissues yielded two molecular mass species (M r 14 000 and 18 500) of AM immunoreactivity in the mammary gland for the above developmental stages, consistent with processed intermediate and prohormone forms respectively. Ovariectomy alone or followed by hormonal treatments did not alter the expression pattern for these two proteins. By Western blot, the fully processed AM form (M r 6000) was identified in milk extracts from lactating glands. These data suggest a potential role for AM and its receptor in the maintenance of mammary gland homeostasis and suggests a potential role for AM in development of the newborn.

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Adrenomedullin Suppresses Mitogenesis in Rat Mesangial Cells via cAMP Pathway

Cited by 143 publications

References 0 publications

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Adrenomedullin Expression in Human Tumor Cell Lines ITS POTENTIAL ROLE AS AN AUTOCRINE GROWTH FACTOR

Adrenomedullin expression in the mouse mammary gland: evidence for the mature form in milk

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