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Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells.

Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Research Abstract Details 

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  • Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Abstract Text:

    s y hanS Y Han,m s leeM S Lee,h r kimH R Kim,s h baekS H Baek,d h ahnD H Ahn,h s chaeH S Chae,r h ericksonR H Erickson,m h sleisengerM H Sleisenger,y s kimY S Kim,

    Phorbol esters such as phorbol 12-myristate 13-acetate (PMA) have been reported to modulate diverse cellular responses through signal transduction pathways including the protein kinase C (PKC) pathway. In the present study, we sought to determine the effect of PMA on mucin gene expression and on the biological properties of a human colon cancer cell line, HM3. The cells were treated for 8 and 24 h with various concentrations of PMA and total RNA was extracted and Northern and slot blot analyses were carried out using MUC2, MUC3 and MUC5AC mucin cDNA probes to assess the steady state levels of mRNA. Spent media were collected and the level of cancer associated carbohydrate antigens (T, Tn, sialyl Tn, sialyl Lex, and sialyl Lea) and matrix-degrading metalloproteinase (MMPs) activity were examined. Trypsinized cells were used for assessing in vitro invasion, motility and adhesion to matrigel. Our results showed that PMA caused upregulation of steady state mRNA levels of MUC2, MUC3 and MUC5AC which was inhibited after treatment with protein synthesis inhibitors. Calphostin C, a highly specific inhibitor of protein kinase C significantly inhibited the PMA induced induction of mRNA levels of MUC2, MUC3, and MUC5AC. The levels of all cancer-associated mucin carbohydrate antigens examined in the media were increased by PMA treatment. PMA also caused an increase in MMPs activity and in in vitro invasion and motility properties, but did not affect adhesion of HM3 cells to matrigel. Thus, PMA caused a significant increase in the expression of all three mucin genes through signaling pathways involving protein kinase C and increased secretion of mucin associated carbohydrate antigens. These changes were associated with increases in MMP activity as well as by increases in the invasive and motility properties of HM3 colon cancer cells. These data suggest that protein kinase C signaling pathways may be involved in mucin gene regulation and in modulating the invasive and metastatic properties of colon cancer cells.

    Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Publishing Authors By Initials

    sy hanSY Han,ms leeMS Lee,hr kimHR Kim,sh baekSH Baek,dh ahnDH Ahn,hs chaeHS Chae,rh ericksonRH Erickson,mh sleisengerMH Sleisenger,ys kimYS Kim,

    For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

    PUBMED ID PMID:

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    Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: International journal of oncology

    VOLUME: 17

    Page Numbers: 487-94

    Journal Abbreviation: Int. J. Oncol.

    ISSN: 1019-6439

    DAY: 1

    MONTH: Sep

    YEAR: 2000

    Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 9306042

    Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Keywords Mesh Terms:

    KEYWORDS: Tumor Cells, Cultured

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells. Information

    Substance Name: Metalloendopeptidases

    Registry Number: EC 3.4.24.-

    Grant and Affiliation Information for Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and biological properties of colon cancer cells.

    AFFILIATION: Gastrointestinal Research Laboratory, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.

    Country: GREECE

    GREECE Research PublicationGREECE Research Publication

    AGENCY: United States NCI

    GRANT: CA24321

    ACRONYM: CA

    MEDLINETA: Int J Oncol

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    DATABASENAME:

    ACCESSION NUMBER:

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