Unique expression pattern of the three insulin receptor family members in the rat mammary gland: Dominance of igf-1r and irr over the ir, and cyclical igf-1r expression

Journal of Applied Toxicology

Volumn 31, Issue 4, 2011, Pages 312-328

  Hvid, Henning ^a,b   Klopfleisch, Robert ^c   Vienberg, Sara ^b   Hansen, Bo F ^b   Thorup, Inger ^b   Jensen, Henrik E ^a   Oleksiewicz, Martin B ^d  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b NOVO NORDISK A S   (Denmark)

^c FREIE UNIVERSITÄT BERLIN   (Germany)

^d INTERCELL AG   (Austria)

Author keywords

IGF 1 receptor; Immunohistochemistry; Insulin receptor; Insulin receptor related receptor; Quantitative RT PCR; Rat mammary gland; Receptor mediated carcinogenicity; Toxicologic pathology

Indexed keywords

ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; INSULIN RECEPTOR; INSULIN RECEPTOR A; INSULIN RECEPTOR B; INSULIN RECEPTOR RELATED RECEPTOR; ISOPROTEIN; MESSENGER RNA; PROGESTERONE RECEPTOR; SOMATOMEDIN C RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BREAST EPITHELIUM; CARCINOGENIC ACTIVITY; COLON; CONNECTIVE TISSUE; CONTROLLED STUDY; ESTRUS CYCLE; FEMALE; IMMUNOHISTOCHEMISTRY; LASER MICRODISSECTION; LIVER; MAMMARY GLAND; NONHUMAN; NUCLEOTIDE SEQUENCE; OVARY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SKELETAL MUSCLE;

ANIMALS; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; ESTROUS CYCLE; FEMALE; IMMUNOHISTOCHEMISTRY; MAMMARY GLANDS, ANIMAL; MAMMARY NEOPLASMS, EXPERIMENTAL; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, IGF TYPE 1; RECEPTOR, INSULIN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

RATTUS;

EID: 79957627295     PISSN: 0260437X     EISSN: 10991263     Source Type: Journal    
DOI: 10.1002/jat.1627     Document Type: Article

References (78)

1. Alvarez P, Spicer LJ, Chase CC, Jr, Payton ME, Hamilton TD, Stewart RE, Hammond AC, Olson TA, Wettemann RP. 2000. Ovarian and endocrine characteristics during an estrous cycle in Angus, Brahman, and Senepol cows in a subtropical environment. J. Anim. Sci. 78: 1291-1302.
2. Bailey CJ, Matty AJ. 1972. Glucose tolerance and plasma insulin of the rat in relation to the oestrous cycle and sex hormones. Horm. Metab. Res. 4: 266-270; doi: 10.1055/s-0028-1094063.
3. Berlato C, Doppler W. 2009. Selective response to insulin versus insulin-like growth factor-I and -II and up-regulation of insulin receptor splice variant B in the differentiated mouse mammary epithelium. Endocrinology 150: 2924-2933; doi: 10.1210/en.2008-0668.
4. Bibby BM, Martinussen T, Skovgaard IM. 2004. Experimental Design in the Agricultural Sciences. Samfundslitteratur: Copenhagen.
5. Bonnesen C, Nelander GM, Hansen BF, Jensen P, Krabbe JS, Jensen MB, Hegelund AC, Svendsen JE, Oleksiewicz MB. 2010. Synchronization in G(0)/G (1) enhances the mitogenic response of cells overexpressing the human insulin receptor A isoform to insulin. Cell Biol. Toxicol. 26: 293-307; doi: 10.1007/s10565-009-9142-x.
6. Brange J, Ribel U, Hansen JF, Dodson G, Hansen MT, Havelund S, Melberg SG, Norris F, Norris K, Snel L. 1988. Monomeric insulins obtained by protein engineering and their medical implications. Nature 333: 679-682; doi: 10.1038/333679a0.
7. Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, Tao N, Rosenfeld-Franklin M, Lerner L, Chiu MI, Wild R, Epstein D, Pachter JA, Miglarese MR. 2010. Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer. Mol. Cancer Ther. 9(10): 2652-2664; doi: 10.1158/1535-7163.MCT-10-0318.
8. Chan MM, Lu X, Merchant FM, Iglehart JD, Miron PL. 2005. Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer. Carcinogenesis 26: 1343-1353; doi: 10.1093/carcin/bgi100.
9. Dideriksen LH, Jorgensen LN, Dreijer K. 1992. Carcinogenic effect on female rats after 12 months administration of insulin analog b10 asp. Diabetes 41(suppl. 1): Abstract 143A.
10. Ding H, Gao XL, Hirschberg R, Vadgama JV, Kopple JD. 1996. Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect. J. Clin. Invest. 97: 1064-1075; doi: 10.1172/JCI118499.
11. Dissen GA, Garcia-Rudaz C, Tapia V, Parada LF, Hsu SY, Ojeda SR. 2006. Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary. Endocrinology 147: 155-165; doi: 10.1210/en.2005-0386.
12. EMEA/CPMP. 2001. Points to consider document on the non-clinical assessment of carcinogenic potential of insulin analogs; available from: (accessed 10 August 2010).
13. FDA. 2005. Pharmacology/Toxicology Review and Evaluation, NDA no. 21-839.
14. Feldman M, Ruan W, Tappin I, Wieczorek R, Kleinberg DL. 1999. The effect of GH on estrogen receptor expression in the rat mammary gland. J. Endocrinol. 163: 515-522; doi: 10.1677/joe.0.1630515.
15. Fleige S, Pfaffl MW. 2006. RNA integrity and the effect on the real-time qRT-PCR performance. Mol. Asp. Med. 27: 126-139; doi: 10.1016/j.mam.2005.12.003.
16. Flint DJ. 1980. Changes in the number of insulin receptors of isolated rat hepatocytes during pregnancy and lactation. Biochim. Biophys. Acta 628: 322-327.
17. Flint DJ. 1982. Insulin binding to rat mammary gland at various stages of cell isolation and purification. Mol. Cell Endocrinol. 26: 281-294.
18. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R. 1999. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol. Cell. Biol. 19: 3278-3288.
19. Gammeltoft S, Hansen BF, Dideriksen L, Lindholm A, Schaffer L, Trub T, Dayan A, Kurtzhals P. 1999. Insulin aspart: a novel rapid-acting human insulin analogue. Expert. Opin. Invest. Drugs 8: 1431-1442.
20. Griffith DR, and Turner CW. 1961. Normal growth of rat mammary glands during pregnancy and early lactation. Proc. Soc. Exp. Biol. Med. 106: 448-450.
21. Hansen BF, Danielsen GM, Drejer K, Sorensen AR, Wiberg FC, Klein HH, Lundemose AG. 1996. Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem. J. 315(Pt 1): 271-279.
22. Hartman CG. 1944. Some new observations on the vaginal smear of the rat. Yale J. Biol. Med. 17: 99-111.
23. Haslam SZ, Shyamala G. 1981. Relative distribution of estrogen and progesterone receptors among the epithelial, adipose, and connective tissue components of the normal mammary gland. Endocrinology 108: 825-830; doi: 10.1210/endo-108-3-825.
24. Humphreys RC, Lydon J, O'Malley BW, Rosen JM. 1997. Mammary gland development is mediated by both stromal and epithelial progesterone receptors. Mol. Endocrinol. 11: 801-811; doi: 10.1210/me.11.6.801.
25. Hungermann D, Buerger H, Oehlschlegel C, Herbst H, Boecker W. 2005. Adenomyoepithelial tumours and myoepithelial carcinomas of the breast - a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells. BMC Cancer 5: 92; doi: 10.1186/1471-2407-5-92.
26. Hvid H, Thorup I, Oleksiewicz MB, Sjogren I, Jensen HE. 2010a. An alternative method for preparation of tissue sections from the rat mammary gland. Exp. Toxicol. Pathol. 1 March [Epub ahead of print]; doi: 10.1016/j.etp.2010.02.005.
27. Hvid H, Ekstrøm CT, Vienberg S, Klopfleisch R. 2010b. Identification of stable and oestrous cycle independent housekeeping-genes in the rat mammary gland and other tissues. Vet. J. 15 October [Epub ahead of print]; doi: 10.1016/j.tvjl.2010.09.002.
28. Jernstrom H, Deal C, Wilkin F, Chu W, Tao Y, Majeed N, Hudson T, Narod SA, Pollak M. 2001. Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women. Cancer Epidemiol. Biomarkers Prev. 10: 377-384.
29. Kacew S, Ruben Z, McConnell RF. 1995. Strain as a determinant factor in the differential responsiveness of rats to chemicals. Toxicol. Pathol. 23: 701-714.
30. Kiunga GA, Raju J, Sabljic N, Bajaj G, Good CK, Bird RP. 2004. Elevated insulin receptor protein expression in experimentally induced colonic tumors. Cancer Lett. 211: 145-153; doi: 10.1016/j.canlet.2004.02.015.
31. Klopfleisch R, Gruber AD. 2009. Increased expression of BRCA2 and RAD51 in lymph node metastases of canine mammary adenocarcinomas. Vet. Pathol. 46: 416-422; doi: 10.1354/vp.08-VP-0212-K-FL.
32. Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T. 2000. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 49: 999-1005; doi: 10.2337/diabetes.49.6.999.
33. Lanzino M, Morelli C, Garofalo C, Panno ML, Mauro L, Ando S, Sisci D. 2008. Interaction between estrogen receptor alpha and insulin/IGF signaling in breast cancer. Curr. Cancer Drug Targets 8: 597-610.
34. Lauritzen HP, Ploug T, Prats C, Tavare JM, Galbo H. 2006. Imaging of insulin signaling in skeletal muscle of living mice shows major role of T-tubules. Diabetes 55: 1300-1306; doi: 10.2337/db05-1216.
35. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25: 402-408; doi: 10.1006/meth.2001.1262.
36. Long JA, Evans HM. 1922. The oestrous cycle in the rat and its associated phenomena. Mem. Univ. Calif. 6: 1-148.
37. Lundby C, Nordsborg N, Kusuhara K, Kristensen KM, Neufer PD, Pilegaard H. 2005. Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies. Eur. J. Appl. Physiol. 95: 351-360; doi: 10.1007/s00421-005-0022-7.
38. Maffini MV, Soto AM, Calabro JM, Ucci AA, Sonnenschein C. 2004. The stroma as a crucial target in rat mammary gland carcinogenesis. J. Cell Sci. 117: 1495-1502; doi: 10.1242/jcs.01000.
39. Mallepell S, Krust A, Chambon P, Brisken C. 2006. Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc. Natl Acad. Sci. USA 103: 2196-2201; doi: 10.1073/pnas.0510974103.
40. Mandl AM. 1951. The phases of the oestrous cycle in the adult white rat. J. Exp. Biol. 28: 576-584.
41. Marcondes FK, Bianchi FJ, Tanno AP. 2002. Determination of the estrous cycle phases of rats: some helpful considerations. Braz. J. Biol. 62: 609-614; doi: 10.1590/S1519-69842002000400008.
42. Masso-Welch PA, Darcy KM, Stangle-Castor NC, Ip MM. 2000. A developmental atlas of rat mammary gland histology. J. Mamm. Gland Biol. Neoplasia 5: 165-185; doi: 10.1023/A:1026491221687.
43. Ministry of Justice. 2003. The Care and Housing of Laboratory Animals/Bekendtgørelse om forsøgsdyrs pasning og opstaldning og om anvendelse af udryddelsestruede og vildtlevende dyr til forsøg mv. BEK no. 687 af 25/7/2003.
44. Missmer SA, Spiegelman D, Bertone-Johnson ER, Barbieri RL, Pollak MN, Hankinson SE. 2006. Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period. Cancer Epidemiol. Biomark. Prev. 15: 972-978; doi: 10.1158/1055-9965.EPI-05-0848.
45. Mueller SO, Clark JA, Myers PH, Korach KS. 2002. Mammary gland development in adult mice requires epithelial and stromal estrogen receptor alpha. Endocrinology 143: 2357-2365; doi: 10.1210/en.143.6.2357.
46. Nakae J, Kido Y, Accili D. 2001. Distinct and overlapping functions of insulin and IGF-I receptors. Endocr. Rev. 22: 818-835; doi: 10.1210/er.22.6.818.
47. Nef S, Verma-Kurvari S, Merenmies J, Vassalli JD, Efstratiadis A, Accili D, Parada LF. 2003. Testis determination requires insulin receptor family function in mice. Nature 426: 291-295; doi: 10.1038/nature02059.
48. Park OK, Mayo KE. 1991. Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge. Mol. Endocrinol. 5: 967-978; doi: 10.1210/mend-5-7-967.
49. Pfaffl M, Bruckmaier R, Windisch W. 2002. Metabolic effects of zinc deficiency on the somatotropic axis in non-growing rats as a new animal model to adult animals. J. Animal Sci. 80(suppl. 1): 351.
50. Prosser CG, Sankaran L, Hennighausen L, Topper YJ. 1987. Comparison of the roles of insulin and insulin-like growth factor I in casein gene expression and in the development of alpha-lactalbumin and glucose transport activities in the mouse mammary epithelial cell. Endocrinology 120: 1411-1416; doi: 10.1210/endo-120-4-1411.
51. Quarrie LH, Addey CV, Wilde CJ. 1996. Programmed cell death during mammary tissue involution induced by weaning, litter removal, and milk stasis. J. Cell Physiol. 168: 559-569.
52. Rakha EA, Putti TC, bd El-Rehim DM, Paish C, Green AR, Powe DG, Lee AH, Robertson JF, Ellis IO. 2006. Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J. Pathol. 208: 495-506; doi: 10.1002/path.1916.
53. Rhoads RE, Grudzien-Nogalska E. 2007. Translational regulation of milk protein synthesis at secretory activation. J. Mamm. Gland. Biol. Neoplasia 12: 283-292; doi: 10.1007/s10911-007-9058-0.
54. Richert MM, Wood TL. 1999. The insulin-like growth factors (IGF) and IGF type I receptor during postnatal growth of the murine mammary gland: sites of messenger ribonucleic acid expression and potential functions. Endocrinology 140: 454-461; doi: 10.1210/en.140.1.454.
55. Rowzee AM, Ludwig DL, Wood TL. 2009. Insulin-like growth factor type 1 receptor and insulin receptor isoform expression and signaling in mammary epithelial cells. Endocrinology 150: 3611-3619; doi: 10.1210/en.2008-1473.
56. Ruan W, Kleinberg DL. 1999. Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology 140: 5075-5081; doi: 10.1210/en.140.11.5075.
57. Ruan W, Catanese V, Wieczorek R, Feldman M, Kleinberg DL. 1995. Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. Endocrinology 136: 1296-1302; doi: 10.1210/en.136.3.1296.
58. Ruan W, Monaco ME, Kleinberg DL. 2005. Progesterone stimulates mammary gland ductal morphogenesis by synergizing with and enhancing insulin-like growth factor-I action. Endocrinology 146: 1170-1178; doi: 10.1210/en.2004-1360.
59. Ruehl-Fehlert C, Kittel B, Morawietz G, Deslex P, Keenan C, Mahrt CR, Nolte T, Robinson M, Stuart BP, Deschl U. 2003. Revised guides for organ sampling and trimming in rats and mice - part 1. Exp. Toxicol. Pathol. 55: 91-106; doi: 10.1078/0940-2993-00311.
60. Russo J, Ao X, Grill C, Russo IH. 1999. Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res. Treat. 53: 217-227; doi: 10.1023/A:1006186719322.
61. Saji S, Jensen EV, Nilsson S, Rylander T, Warner M, Gustafsson JA. 2000. Estrogen receptors alpha and beta in the rodent mammary gland. Proc. Natl Acad. Sci. USA 97: 337-342.
62. Sakaguchi H, Fujimoto J, Hong BL, Tamaya T. 2005. Quantitative analysis of estrogen receptor proteins in rat ovary. J. Steroid Biochem. Mol. Biol. 94: 83-91; doi: 10.1016/j.jsbmb.2004.12.034.
63. Sapino A, Papotti M, Sanfilippo B, Gugliotta P, Bussolati G. 1992. Tumor types derived from epithelial and myoepithelial cell lines of R3230AC rat mammary carcinoma. Cancer Res. 52: 1553-1560.
64. Schedin P, Mitrenga T, Kaeck M. 2000. Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague-Dawley rat: a model for investigating the role of estrous cycling in mammary carcinogenesis. J. Mamm. Gland Biol. Neoplasia 5: 211-225; doi: 10.1023/A:1026447506666.
65. Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. 2006. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol. Biol. 7: 3; doi: 10.1186/1471-2199-7-3.
66. Selvamani A, Sohrabji F. 2010. The neurotoxic effects of estrogen on ischemic stroke in older female rats is associated with age-dependent loss of insulin-like growth factor-1. J. Neurosci. 30: 6852-6861; doi: 10.1523/JNEUROSCI.0761-10.2010.
67. Serrano R, Villar M, Martinez C, Carrascosa JM, Gallardo N, Andres A. 2005. Differential gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat adipose tissue. J. Mol. Endocrinol. 34: 153-161; doi: 10.1677/jme.1.01635.
68. Shier P, Watt VM. 1992. Tissue-specific expression of the rat insulin receptor-related receptor gene. Mol. Endocrinol. 6: 723-729; doi: 10.1210/me.6.5.723.
69. Slieker LJ, Brooke GS, DiMarchi RD, Flora DB, Green LK, Hoffmann JA, Long HB, Fan L, Shields JE, Sundell KL, Surface PL, Chance RE. 1997. Modifications in the B10 and B26-30 regions of the B chain of human insulin alter affinity for the human IGF-I receptor more than for the insulin receptor. Diabetologia 40(suppl. 2): S54-S61.
70. Strange R, Westerlind KC, Ziemiecki A, Andres AC. 2007. Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle. Acta Physiol. 190: 137-149; doi: 10.1111/j.1748-1716.2007.01704.x.
71. Tennekes H, Gembardt C, Dammann M, Van RB. 2004. The stability of historical control data for common neoplasms in laboratory rats: adrenal gland (medulla), mammary gland, liver, endocrine pancreas, and pituitary gland. Regul. Toxicol. Pharmacol. 40: 18-27; doi: 10.1016/j.yrtph.2004.04.003.
72. Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le BT, Kathuria S, Chen E. 1986. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 5: 2503-2512.
73. Vandesompele J, De PK, Pattyn F, Poppe B, van Roy N, De PA, Speleman F. 2002. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3: research0034.1-0034.11; doi: 10.1186/gb-2002-3-7-research0034.
74. Westwood FR. 2008. The female rat reproductive cycle: a practical histological guide to staging. Toxicol. Pathol. 36: 375-384; doi: 10.1177/0192623308315665.
75. Wiseman BS, Werb Z. 2002. Stromal effects on mammary gland development and breast cancer. Science 296: 1046-1049; doi: 10.1126/science.1067431.
76. Zeps N, Bentel JM, Papadimitriou JM, Dawkins HJ. 1999. Murine progesterone receptor expression in proliferating mammary epithelial cells during normal pubertal development and adult estrous cycle. Association with eralpha and erbeta status. J. Histochem. Cytochem. 47: 1323-1330.
77. Zhu M, de Carbo R, Anson RM, Ingram DK, Lane MA. 2005. Caloric restriction modulates insulin receptor signaling in liver and skeletal muscle of rat. Nutrition 21: 378-388; doi: 10.1016/j.nut.2004.06.030.
78. Zimmermann JL, Truex LL. 1997. 12-Month chronic toxicity study of LY275585 (human insulin analog) administered subcutaneously to Fischer 344 Rats. Int. J. Toxicol. 16: 639-657.