Liver, Pancreas, and Biliary TractBone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo☆,☆☆
Section snippets
Materials
The following materials were purchased: fetal bovine serum, Dulbecco's modified Eagle medium (DMEM), trypsin solution, and penicillin-streptomycin solution from Irvine Scientific (Santa Ana, CA); Genescreen membranes from New England Nuclear (Boston, MA); restriction enzymes, Genius 3 nucleic acid detection kit, and random primed labeling kit from Boehringer Mannheim (Indianapolis, IN); Sequenase version 2.0 DNA Sequencing from United States Biochemical (Cleveland, OH); [α-32P]deoxycytidine
Expression of BMP-2, BMPR-IA, BMPR-IB, and BMPR-II in human pancreatic tissues
Northern blot analysis of total RNA isolated from normal human pancreatic tissue revealed a faint BMP-2 messenger RNA (mRNA) transcript (approximately 3.4 kb)26 that was visible on the original autoradiographs in 11 of 12 normal pancreatic samples (Figure 1) and in 12 of 14 chronic pancreatitis samples (Figure 2A).
Discussion
BMP-2 is synthesized as a large precursor that is processed to yield the active BMP-2 protein dimer.6 BMP-2 was originally isolated as a peptide capable of inducing ectopic cartilage formation in vivo.5 BMP-2 is now known to participate in many biological processes in both vertebrates and invertebrates.5 BMP expression has been reported in prostate,33, 34 gastric,35 colorectal, thyroid, and bladder cancer cell lines.36 Expression of BMPs has also been observed in human tumors such as prostate
Acknowledgements
The authors thank Prof. Dr. J. Husler and A. Gemperli, Department of Mathematical Statistics, University of Bern, Switzerland, for statistical support.
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2017, Seminars in Cancer BiologyCitation Excerpt :The first extensive analysis of PDAC protein-coding exomes was performed in the tumor tissues of 24 PDAC patients (including 9 cases from already metastasized PDAC) [63], and revealed previously unrecognized genetic alterations, such as aberrations in bone morphogenetic protein 2 (BMP2). Members of the BMP family are thought to contribute to the osteosclerotic lesions frequently observed in metastatic prostate cancer and high levels of expression of BMP2 are correlated with shorter postoperative survival in PDAC patients [64]. Of note, several genes that participate in the DNA damage response, such as PARP1, BRCA1, ATM and TP53, have been associated with metastasis by a number of in vitro biochemical and cellular assays.
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2017, Cytokine and Growth Factor ReviewsCitation Excerpt :Pancreatic cancers showed a 12.5-fold, 2-fold, and 8-fold increase of BMP-2, BMP receptor (R)-IA, and BMPR-II messenger RNA levels respectively, compared to normal pancreas. It was also confirmed by immunohistochemistry and in situ hybridization that BMP-2 was expressed in the cancer cells within the tumor mass [84]. Kleeff et al. further reported that BMP-2 stimulated the growth of two pancreatic cancer cell lines, ASPC-1 and CAPAN-1, inhibited the growth of COLO-357 cells, another pancreatic cancer cell line, and had no effect on three other pancreatic cancer cell lines (MIA-PaCa-2, PANC-1, and T3M4) that underexpressed either the BMP receptors or Smad1.They suggested that BMP-2 may have the capacity to act as a mitogen when Smad4 is mutated [84].
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Address requests for reprints to: Murray Korc, M.D., Division of Endocrinology, Diabetes and Metabolism, Medical Sciences I, C240, University of California, Irvine, California 92697. e-mail: [email protected]; fax: (949) 824-1035.
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Supported by U.S. Public Health Service grants CA-75059 and CA-40162 (to M.K.) and by a fellowship award from the University of California Research and Education Grant on Gene Therapy for Cancer (to J.K.).