• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Aug 1990; 10(8): 4027–4034.
PMCID: PMC360913

Epidermal growth factor receptor, but not c-erbB-2, activation prevents lactogenic hormone induction of the beta-casein gene in mouse mammary epithelial cells.

Abstract

The HC11 cell line was isolated from mammary gland cells of pregnant mice. The cells displayed a normal phenotype and retained some characteristics of mammary epithelial cell differentiation. After treatment with the lactogenic hormones prolactin and glucocorticoids, the HC11 cells expressed the milk protein beta-casein. Various oncogenes were transfected and expressed in HC11 cells. The oncogenes were tested for their transformation ability and for their effects upon the differentiation of the HC11 cells. All of the oncogenes tested, including activated human Ha-ras, human transforming growth factor-alpha, activated rat neuT, and human c-erbB-2 activated by a point mutation in the transmembrane domain, caused transformation of the HC11 cells, as shown by tumor formation in nude mice. HC11 cells expressing the neuT and activated c-erbB-2 genes synthesized beta-casein in response to lactogenic hormones, whereas those expressing the Ha-ras or transforming growth factor-alpha oncogenes were no longer able to respond to the lactogenic hormones. This inhibition of beta-casein production occurs at the transcriptional level and in the transforming growth factor-alpha-transformed cells is due to an autocrine mechanism involving the activation of the epidermal growth factor receptor. This suggests that, although the c-erbB-2 and epidermal growth factor receptors are structurally quite similar, their activation has different effects upon mammary epithelial cell differentiation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anzano MA, Roberts AB, De Larco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Lazarus JE, Sporn MB. Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol. 1985 Jan;5(1):242–247. [PMC free article] [PubMed]
  • Ball RK, Friis RR, Schoenenberger CA, Doppler W, Groner B. Prolactin regulation of beta-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J. 1988 Jul;7(7):2089–2095. [PMC free article] [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. [PubMed]
  • Bar-Sagi D, Feramisco JR. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. [PubMed]
  • Bates SE, Davidson NE, Valverius EM, Freter CE, Dickson RB, Tam JP, Kudlow JE, Lippman ME, Salomon DS. Expression of transforming growth factor alpha and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Mol Endocrinol. 1988 Jun;2(6):543–555. [PubMed]
  • Berger MS, Locher GW, Saurer S, Gullick WJ, Waterfield MD, Groner B, Hynes NE. Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 1988 Mar 1;48(5):1238–1243. [PubMed]
  • Chamberlain JP. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. [PubMed]
  • Church GM, Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. [PMC free article] [PubMed]
  • Ciardiello F, Hynes N, Kim N, Valverius EM, Lippman ME, Salomon DS. Transformation of mouse mammary epithelial cells with the Ha-ras but not with the neu oncogene results in a gene dosage-dependent increase in transforming growth factor-alpha production. FEBS Lett. 1989 Jul 3;250(2):474–478. [PubMed]
  • Ciardiello F, Kim N, Hynes N, Jaggi R, Redmond S, Liscia DS, Sanfilippo B, Merlo G, Callahan R, Kidwell WR, et al. Induction of transforming growth factor alpha expression in mouse mammary epithelial cells after transformation with a point-mutated c-Ha-ras protooncogene. Mol Endocrinol. 1988 Dec;2(12):1202–1216. [PubMed]
  • Danielson KG, Oborn CJ, Durban EM, Butel JS, Medina D. Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3756–3760. [PMC free article] [PubMed]
  • Di Marco E, Pierce JH, Fleming TP, Kraus MH, Molloy CJ, Aaronson SA, Di Fiore PP. Autocrine interaction between TGF alpha and the EGF-receptor: quantitative requirements for induction of the malignant phenotype. Oncogene. 1989 Jul;4(7):831–838. [PubMed]
  • Doppler W, Groner B, Ball RK. Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat beta-casein gene promoter constructs in a mammary epithelial cell line. Proc Natl Acad Sci U S A. 1989 Jan;86(1):104–108. [PMC free article] [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. [PubMed]
  • Guérin M, Barrois M, Terrier MJ, Spielmann M, Riou G. Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis. Oncogene Res. 1988;3(1):21–31. [PubMed]
  • Gullick WJ, Berger MS, Bennett PL, Rothbard JB, Waterfield MD. Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer. 1987 Aug 15;40(2):246–254. [PubMed]
  • Gültekin H, Heermann KH. The use of polyvinylidenedifluoride membranes as a general blotting matrix. Anal Biochem. 1988 Aug 1;172(2):320–329. [PubMed]
  • Gusterson BA, Machin LG, Gullick WJ, Gibbs NM, Powles TJ, Elliott C, Ashley S, Monaghan P, Harrison S. c-erbB-2 expression in benign and malignant breast disease. Br J Cancer. 1988 Oct;58(4):453–457. [PMC free article] [PubMed]
  • Hudziak RM, Schlessinger J, Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159–7163. [PMC free article] [PubMed]
  • Hynes NE, Gerber HA, Saurer S, Groner B. Overexpression of the c-erbB-2 protein in human breast tumor cell lines. J Cell Biochem. 1989 Feb;39(2):167–173. [PubMed]
  • Hynes NE, Jaggi R, Kozma SC, Ball R, Muellener D, Wetherall NT, Davis BW, Groner B. New acceptor cell for transfected genomic DNA: oncogene transfer into a mouse mammary epithelial cell line. Mol Cell Biol. 1985 Jan;5(1):268–272. [PMC free article] [PubMed]
  • Lee J, Dull TJ, Lax I, Schlessinger J, Ullrich A. HER2 cytoplasmic domain generates normal mitogenic and transforming signals in a chimeric receptor. EMBO J. 1989 Jan;8(1):167–173. [PMC free article] [PubMed]
  • Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS, Kidwell WR. Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production. Mol Endocrinol. 1987 Oct;1(10):683–692. [PubMed]
  • Masuko T, Sugahara K, Kozono M, Otsuki S, Akiyama T, Yamamoto T, Toyoshima K, Hashimoto Y. A murine monoclonal antibody that recognizes an extracellular domain of the human c-erbB-2 protooncogene product. Jpn J Cancer Res. 1989 Jan;80(1):10–14. [PubMed]
  • Olson EN, Capetanaki YG. Developmental regulation of intermediate filament and actin mRNAs during myogenesis is disrupted by oncogenic ras genes. Oncogene. 1989 Jul;4(7):907–913. [PubMed]
  • Perroteau I, Salomon D, DeBortoli M, Kidwell W, Hazarika P, Pardue R, Dedman J, Tam J. Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat. 1986;7(3):201–210. [PubMed]
  • Reddel RR, Ke Y, Kaighn ME, Malan-Shibley L, Lechner JF, Rhim JS, Harris CC. Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: altered response to inducers of terminal squamous differentiation. Oncogene Res. 1988;3(4):401–408. [PubMed]
  • Redmond SM, Reichmann E, Müller RG, Friis RR, Groner B, Hynes NE. The transformation of primary and established mouse mammary epithelial cells by p21-ras is concentration dependent. Oncogene. 1988 Mar;2(3):259–265. [PubMed]
  • Rosenthal A, Lindquist PB, Bringman TS, Goeddel DV, Derynck R. Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation. Cell. 1986 Jul 18;46(2):301–309. [PubMed]
  • Salomon DS, Perroteau I, Kidwell WR, Tam J, Derynck R. Loss of growth responsiveness to epidermal growth factor and enhanced production of alpha-transforming growth factors in ras-transformed mouse mammary epithelial cells. J Cell Physiol. 1987 Mar;130(3):397–409. [PubMed]
  • Segatto O, King CR, Pierce JH, Di Fiore PP, Aaronson SA. Different structural alterations upregulate in vitro tyrosine kinase activity and transforming potency of the erbB-2 gene. Mol Cell Biol. 1988 Dec;8(12):5570–5574. [PMC free article] [PubMed]
  • Shih C, Weinberg RA. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. [PubMed]
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. [PubMed]
  • Southern PJ, Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed]
  • Sternberg EA, Spizz G, Perry ME, Olson EN. A ras-dependent pathway abolishes activity of a muscle-specific enhancer upstream from the muscle creatine kinase gene. Mol Cell Biol. 1989 Feb;9(2):594–601. [PMC free article] [PubMed]
  • Sukumar S, Notario V, Martin-Zanca D, Barbacid M. Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations. Nature. 1983 Dec 15;306(5944):658–661. [PubMed]
  • Topper YJ, Freeman CS. Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev. 1980 Oct;60(4):1049–1106. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Tremblay PJ, Pothier F, Hoang T, Tremblay G, Brownstein S, Liszauer A, Jolicoeur P. Transgenic mice carrying the mouse mammary tumor virus ras fusion gene: distinct effects in various tissues. Mol Cell Biol. 1989 Feb;9(2):854–859. [PMC free article] [PubMed]
  • van de Vijver MJ, Peterse JL, Mooi WJ, Wisman P, Lomans J, Dalesio O, Nusse R. Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med. 1988 Nov 10;319(19):1239–1245. [PubMed]
  • van de Vijver M, van de Bersselaar R, Devilee P, Cornelisse C, Peterse J, Nusse R. Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. Mol Cell Biol. 1987 May;7(5):2019–2023. [PMC free article] [PubMed]
  • Vonderhaar BK. Regulation of development of the normal mammary gland by hormones and growth factors. Cancer Treat Res. 1988;40:251–266. [PubMed]
  • Wong ST, Winchell LF, McCune BK, Earp HS, Teixidó J, Massagué J, Herman B, Lee DC. The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction. Cell. 1989 Feb 10;56(3):495–506. [PubMed]
  • Zhou D, Battifora H, Yokota J, Yamamoto T, Cline MJ. Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer. Cancer Res. 1987 Nov 15;47(22):6123–6125. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...