Functional analysis of the 5′-flanking region of the human gastrin-releasing peptide gene in small cell lung carcinoma cell lines

Srinivasa R. Nagalla, Eliot Spindel

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    The mammalian bombesin-like peptide, gastrin-releasing peptide (GRP), is expressed by many small cell lung carcinomas (SCLC), stimulates the growth of some SCLC and thus is an autocrine growth factor for a subset of SCLC. The subset of SCLC that expresses GRP typically shows neuroendocrine differentiation and has been designated as "classic" SCLC. To begin to characterize the mechanisms responsible for the expression of GRP in classic SCLC, the 5′-flanking region of the human GRP gene was sequenced and analyzed for cis-acting elements. Constructs containing up to 6.0 kilobases of 5′-flanking region were transiently expressed in SCLC and in control cell lines. Deletion analysis demonstrated that a sequence of 178 bases upstream of the transcriptional start was sufficient for basal expression in SCLC cell lines. A negative regulatory element was located between -5.5 and -2.6 kilobases; a general enhancer element was located between -1409 and -1197 kilobases, and a tissue-specific element was located between -1128 and -793 kilobases. Mobility shift analysis indicated that proteins from nuclear extracts of classic SCLC but not variant SCLC bound to this tissue-specific regulator, element. Thus the regulation of GRP gene expression in SCLC cell lines is a balance between a negative element, a general enhancer, and a tissue-specific element that appears active only in classic SCLC cell lines.

    Original languageEnglish (US)
    Pages (from-to)4461-4467
    Number of pages7
    JournalCancer Research
    Volume54
    Issue number16
    StatePublished - Aug 15 1994

    Fingerprint

    Gastrin-Releasing Peptide
    5' Flanking Region
    Small Cell Lung Carcinoma
    Cell Line
    Genes
    Bombesin
    Nuclear Proteins

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Functional analysis of the 5′-flanking region of the human gastrin-releasing peptide gene in small cell lung carcinoma cell lines. / Nagalla, Srinivasa R.; Spindel, Eliot.

    In: Cancer Research, Vol. 54, No. 16, 15.08.1994, p. 4461-4467.

    Research output: Contribution to journalArticle

    @article{c5c44145f5f0473fb9027c1c283ea48d,
    title = "Functional analysis of the 5′-flanking region of the human gastrin-releasing peptide gene in small cell lung carcinoma cell lines",
    abstract = "The mammalian bombesin-like peptide, gastrin-releasing peptide (GRP), is expressed by many small cell lung carcinomas (SCLC), stimulates the growth of some SCLC and thus is an autocrine growth factor for a subset of SCLC. The subset of SCLC that expresses GRP typically shows neuroendocrine differentiation and has been designated as {"}classic{"} SCLC. To begin to characterize the mechanisms responsible for the expression of GRP in classic SCLC, the 5′-flanking region of the human GRP gene was sequenced and analyzed for cis-acting elements. Constructs containing up to 6.0 kilobases of 5′-flanking region were transiently expressed in SCLC and in control cell lines. Deletion analysis demonstrated that a sequence of 178 bases upstream of the transcriptional start was sufficient for basal expression in SCLC cell lines. A negative regulatory element was located between -5.5 and -2.6 kilobases; a general enhancer element was located between -1409 and -1197 kilobases, and a tissue-specific element was located between -1128 and -793 kilobases. Mobility shift analysis indicated that proteins from nuclear extracts of classic SCLC but not variant SCLC bound to this tissue-specific regulator, element. Thus the regulation of GRP gene expression in SCLC cell lines is a balance between a negative element, a general enhancer, and a tissue-specific element that appears active only in classic SCLC cell lines.",
    author = "Nagalla, {Srinivasa R.} and Eliot Spindel",
    year = "1994",
    month = "8",
    day = "15",
    language = "English (US)",
    volume = "54",
    pages = "4461--4467",
    journal = "Journal of Cancer Research",
    issn = "0099-7013",
    publisher = "American Association for Cancer Research Inc.",
    number = "16",

    }

    TY - JOUR

    T1 - Functional analysis of the 5′-flanking region of the human gastrin-releasing peptide gene in small cell lung carcinoma cell lines

    AU - Nagalla, Srinivasa R.

    AU - Spindel, Eliot

    PY - 1994/8/15

    Y1 - 1994/8/15

    N2 - The mammalian bombesin-like peptide, gastrin-releasing peptide (GRP), is expressed by many small cell lung carcinomas (SCLC), stimulates the growth of some SCLC and thus is an autocrine growth factor for a subset of SCLC. The subset of SCLC that expresses GRP typically shows neuroendocrine differentiation and has been designated as "classic" SCLC. To begin to characterize the mechanisms responsible for the expression of GRP in classic SCLC, the 5′-flanking region of the human GRP gene was sequenced and analyzed for cis-acting elements. Constructs containing up to 6.0 kilobases of 5′-flanking region were transiently expressed in SCLC and in control cell lines. Deletion analysis demonstrated that a sequence of 178 bases upstream of the transcriptional start was sufficient for basal expression in SCLC cell lines. A negative regulatory element was located between -5.5 and -2.6 kilobases; a general enhancer element was located between -1409 and -1197 kilobases, and a tissue-specific element was located between -1128 and -793 kilobases. Mobility shift analysis indicated that proteins from nuclear extracts of classic SCLC but not variant SCLC bound to this tissue-specific regulator, element. Thus the regulation of GRP gene expression in SCLC cell lines is a balance between a negative element, a general enhancer, and a tissue-specific element that appears active only in classic SCLC cell lines.

    AB - The mammalian bombesin-like peptide, gastrin-releasing peptide (GRP), is expressed by many small cell lung carcinomas (SCLC), stimulates the growth of some SCLC and thus is an autocrine growth factor for a subset of SCLC. The subset of SCLC that expresses GRP typically shows neuroendocrine differentiation and has been designated as "classic" SCLC. To begin to characterize the mechanisms responsible for the expression of GRP in classic SCLC, the 5′-flanking region of the human GRP gene was sequenced and analyzed for cis-acting elements. Constructs containing up to 6.0 kilobases of 5′-flanking region were transiently expressed in SCLC and in control cell lines. Deletion analysis demonstrated that a sequence of 178 bases upstream of the transcriptional start was sufficient for basal expression in SCLC cell lines. A negative regulatory element was located between -5.5 and -2.6 kilobases; a general enhancer element was located between -1409 and -1197 kilobases, and a tissue-specific element was located between -1128 and -793 kilobases. Mobility shift analysis indicated that proteins from nuclear extracts of classic SCLC but not variant SCLC bound to this tissue-specific regulator, element. Thus the regulation of GRP gene expression in SCLC cell lines is a balance between a negative element, a general enhancer, and a tissue-specific element that appears active only in classic SCLC cell lines.

    UR - http://www.scopus.com/inward/record.url?scp=0028100717&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0028100717&partnerID=8YFLogxK

    M3 - Article

    C2 - 8044796

    AN - SCOPUS:0028100717

    VL - 54

    SP - 4461

    EP - 4467

    JO - Journal of Cancer Research

    JF - Journal of Cancer Research

    SN - 0099-7013

    IS - 16

    ER -