Elevated insulin receptor content in human breast cancer
Open accessAbstract
The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Insulin receptors are frequently expressed by breast cancer cells.
“As has been found in other cancers, insulin receptors are frequently expressed by breast cancer cells (59).”
From Diabetes and Cancer (2010) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian Cancer
Slamon, D. J., Godolphin, W. J., Jones, L. A., Holt, J. A., Wong, S., Keith, D. E., Levin, W. J., Stuart, S. G., Udove, J. A., Ullrich, A., et al. (1989) · Science · doi:10.1126/science.2470152 · Cited by 6,817 · see citing works
A simple, rapid, and sensitive DNA assay procedure
Labarca, C. G., & Paigen, K. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90165-7 · Cited by 4,905 · see citing works
Classical and Modern Regression With Applications.
Steinhorst, R. K., & Myers, R. H. (1988) · Journal of the American Statistical Association · doi:10.2307/2288958 · Cited by 3,705 · see citing works
Histological Grading and Prognosis in Breast Cancer
Bloom, H. J. G., & Richardson, W. (1957) · British Journal of Cancer · doi:10.1038/bjc.1957.43 · Cited by 2,938 · see citing works
Estrogenic Regulation of Growth and Polypeptide Growth Factor Secretion in Human Breast Carcinoma
Dickson, R. B., & Lippman, M. E. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-1-29 · Cited by 566 · see citing works
Structural Rearrangement of the Retinoblastoma Gene in Human Breast Carcinoma
Tang, A., Varley, J. M., Chakraborty, S., Murphree, A. L., & Fung, Y.-K. T. (1988) · Science · doi:10.1126/science.3175651 · Cited by 403 · see citing works
Yee, D., Paik, S., Lebovic, G. S., Marcus, R. R., Favoni, R. E., Cullen, K. J., Lippman, M. E., & Rosen, N. X. (1989) · Molecular Endocrinology · doi:10.1210/mend-3-3-509 · Cited by 398 · see citing works
Human breast carcinoma cells in continuous culture: a review.
Engel, L. W., & Young, N. A. (1978) · PubMed · Cited by 345 · see citing works
Furlanetto, R. W., & DiCarlo, J. N. (1984) · PubMed · Cited by 254 · see citing works
van der Burg, B., Rutteman, G. R., Blankenstein, M. A., de Laat, S. W., & van Zoelen, E. J. J. (1988) · Journal of Cellular Physiology · doi:10.1002/jcp.1041340112 · Cited by 247 · see citing works
Amplification of c-erbB-2 and Aggressive Human Breast Tumors?
Ali, I. U., Campbell, G., Lidereau, R., et al. (1988) · Science · doi:10.1126/science.3289120 · Cited by 236 · see citing works
Hormone responsive human breast cancer in long-term tissue culture: effect of insulin.
Osborne, C. K., BOLAN, G. A., Monaco, M. E., & Lippman, M. E. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.12.4536 · Cited by 222 · see citing works
Pekonen, F., Partanen, S., Mäkinen, T., & Rutanen, E. ‐. (1988) · PubMed · Cited by 208 · see citing works
Classical and Modern Regression with Applications
Cornell, J. A., & Myers, R. H. (1987) · Technometrics · doi:10.2307/1269347 · Cited by 154 · see citing works
Cell Proliferation of Estrogen-Sensitive Cells: The Case for Negative Control*
Soto, A. M., & Sonnenschein, C. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-1-44 · Cited by 153 · see citing works
Ck, O., Me, M., Lippman, M. E., et al. (1978) · PubMed · Cited by 133 · see citing works
Forsayeth, J., MONTEMURRO, A., Maddux, B. A., et al. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61322-5 · Cited by 110 · see citing works
Lippman, M. E., & Allegra, J. C. (1980) · Cancer · doi:10.1002/1097-0142(19801215)46:12+ · Cited by 108 · see citing works
Prolactin receptors in human breast cancer cells in long-term tissue culture.
Shiu, R. P. C. (1979) · PubMed · Cited by 105 · see citing works
Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue.
Hennipman, A., van Oirschot, B. A., Smits, J., et al. (1989) · PubMed · Cited by 105 · see citing works
Tamoxifen in the Treatment of Breast Cancer
Legha, S. S. (1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-109-3-219 · Cited by 103 · see citing works
In Vitro Model Systems for the Study of Hormone-Dependent Human Breast Cancer
Bleich, H. L., Boro, E. S., Lippman, M. E., Osborne, C. K., Knazek, R. A., & Young, N. (1977) · New England Journal of Medicine · doi:10.1056/nejm197701202960307 · Cited by 88 · see citing works
Hormone binding by human mammary carcinoma.
Holdaway, I. M., & Friesen, H. G. (1977) · PubMed · Cited by 78 · see citing works
Characterization of insulin-like growth factor I (IGF-I) receptors of human breast cancer cells
Pollak, M., Polychronakos, C., Yousefi, S., et al. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(88)90688-2 · Cited by 75 · see citing works
Biosynthesis and Processing of the Human Insulin Receptor
Forsayeth, J., Maddux, B. A., & Goldfine, I. D. (1986) · Diabetes · doi:10.2337/diab.35.7.837 · Cited by 58 · see citing works
Self-citationCell proliferation induced by insulin in organ culture of rat mammary carcinoma
Heuson, J. C., Coune, A., & Heimann, R. (1967) · Experimental Cell Research · doi:10.1016/0014-4827(67)90185-1 · Cited by 57 · see citing works
Kopersztych, S., Rezkallah-Iwasso, M. T., Miki, S. S., Naspitz, C. K., & Mendes, N. F. (1976) · Cancer · doi:10.1002/1097-0142(197609)38:3 · Cited by 56 · see citing works
Nuclear thyroid hormone receptors in a human breast cancer cell line.
Burke, R. E., & McGuire, W. L. (1978) · PubMed · Cited by 54 · see citing works
Biological markers for breast carcinoma
Waalkes, T. P., Enterline, J. P., Shaper, J. H., Abeloff, M. D., & Ettinger, D. S. (1984) · Cancer · doi:10.1002/1097-0142(19840201)53:3+ · Cited by 49 · see citing works
Estrogen and oncogene mediated growth regulation of human breast cancer cells
Kasid, A., & Lippman, M. E. (1987) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(87)90341-4 · Cited by 46 · see citing works
Histological grading in breast cancer.
Tough, I. C., Carter, D. C., Fraser, J. D., et al. (1969) · British Journal of Cancer · doi:10.1038/bjc.1969.39 · Cited by 43 · see citing works
Perturbation by insulin of human breast cancer cell cycle kinetics.
Gross, G. E., Boldt, D. H., & Osborne, C. K. (1984) · PubMed · Cited by 42 · see citing works
Immunostaining of transferrin and transferrin receptor in human seminiferous tubules
Vannelli, B., Orlando, C., Barni, T., et al. (1986) · Fertility and Sterility · doi:10.1016/s0015-0282(16)49284-8 · Cited by 42 · see citing works
Insulin receptor regulation in cultured human tumor cells.
Mountjoy, K. G., Holdaway, I. M., & Finlay, G. J. (1983) · PubMed · Cited by 40 · see citing works
Human insulin receptor radioimmunoassay: applicability to insulin-resistant states
PEZZINO, V., Papa, V., Trischitta, V., et al. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.257.3.e451 · Cited by 40 · see citing works
Self-citationMountjoy, K. G., Finlay, G. J., & Holdaway, I. M. (1987) · PubMed · Cited by 32 · see citing works
Correlation between hormone binding and growth response of rat mammary tumor.
Holdaway, I. M., & Friesen, H. G. (1976) · PubMed · Cited by 32 · see citing works
Harmon, J. T., & Hilf, R. (1976) · PubMed · Cited by 26 · see citing works
Growth regulation of human breast cancer.
Lippman, M. E. (1985) · PubMed · Cited by 26 · see citing works
Shafie, S. M., & Hilf, R. (1978) · PubMed · Cited by 25 · see citing works
Insulin and glucagon receptors in Morris hepatomas of varying growth rates.
PEZZINO, V., Vigneri, R., Siperstein, M. D., et al. (1979) · PubMed · Cited by 23 · see citing works
Self-citationInfluence of hormones on DNA synthesis of breast tumors in culture
Calaf, G. M., Garrido, F., Moyano, C., et al. (1986) · Breast Cancer Research and Treatment · doi:10.1007/bf01807335 · Cited by 21 · see citing works
Regulation of insulin binding to human mammary carcinoma.
Benson, E. A., & Holdaway, I. M. (1982) · PubMed · Cited by 17 · see citing works
Biosynthesis and processing of the human insulin receptor
Forsayeth, J., Maddux, B. A., & Goldfine, I. D. (1986) · Diabetes · doi:10.2337/diabetes.35.7.837 · Cited by 9 · see citing works
Self-citationIacobelli, S., & Natoli, C. (1985) · Breast Cancer Research and Treatment · doi:10.1007/bf01806777 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Scholl, S., and M. E. Lippmann. 1984. Methods and clinical use of receptor assay. In Breast Cancer: Diagnosis and Management. G. Bonadonna, editor. John Wiley & Sons, New York. 74-108.
- Legha, S. S. 1988. Tamoxifen in the treatment ofbreast cancer. Annals Intern. Med. 109:219-228.
- DeVita V. T., Jr., S. Hellman, and S. A. Rosenberg, editors. J. B. Lippincott Co., Philadelphia. 49-65.
- Sternberger, L. A. 1979. The unlabeled antibody peroxidase- antiperoxidase (PAP) method. In Immunocytochemistry. L. A. Stem- berger, editor. John Wiley & Sons, New York. 104-112.
Cited by
Sorted by citations
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366 · see citing works
Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0087 · Cited by 1,009 · see citing works
Insulin resistance and cancer risk: An overview of the pathogenetic mechanisms
Arcidiacono, B., Iiritano, S., Nocera, A., Possidente, K., Nevolo, M. T., Ventura, V., Foti, D., Chiefari, E., & Brunetti, A. (2012) · Experimental Diabetes Research · doi:10.1155/2012/789174 · Cited by 606 · see citing works
Obesity and cancer: existing and new hypotheses for a causal connection
Stone, T. W., McPherson, M., & Gail Darlington, L. (2018) · eBioMedicine · doi:10.1016/j.ebiom.2018.02.022 · Cited by 262 · see citing works
Challenges and Perspectives in the Treatment of Diabetes Associated Breast Cancer
Samuel, S. M., Varghese, E., Varghese, S., & Büsselberg, D. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.08.004 · Cited by 141 · see citing works
Shukla, A., Grisouard, J., Ehemann, V., Hermani, A., Enzmann, H., & Mayer, D. (2009) · Endocrine Related Cancer · doi:10.1677/erc-08-0240 · Cited by 130 · see citing works
Dowling, R. J., Niraula, S., Chang, M. C., Done, S. J., Ennis, M., McCready, D. R., Leong, W. L., Escallon, J. M., Reedijk, M., Goodwin, P. J., et al. (2015) · Breast Cancer Research · doi:10.1186/s13058-015-0540-0 · Cited by 117 · see citing works
Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer
Mulligan, A. M., O’Malley, F. P., Ennis, M., Fantus, I. G., & Goodwin, P. J. (2007) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9471-x · Cited by 96 · see citing works
Paonessa, F., Foti, D., Costa, V., Chiefari, E., Brunetti, G., Leone, F., Luciano, F., Wu, F., Lee, A. S., Gulletta, E., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3678 · Cited by 52 · see citing works
- Authors
- Papa, V, Pezzino, V, Costantino, A., Belfiore, A., Giuffrida, D., Frittitta, L., Vannelli, G. B., Brand, R., Goldfine, I. D., & Vigneri, R.
- Affiliations
- University of Catania (IT)
- University of California, San Francisco (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1990-11-01
- Volume
- 86
- Issue
- 5
- Pages
- 1503-1510
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296896
- OpenAlex
- W1984532045
- Cited by
- 338
- References
- 46
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 19 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 12 · 2015: 16 · 2014: 13 · 2013: 19 · 2012: 17
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Associazione Italiana per la Ricerca sul Cancro
- Regione Siciliana
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- insulin receptor, breast cancer, insulin receptor tyrosine kinase, tumor growth control, estrogen receptor, tumor size, histological grading, malignant epithelial cells, radioimmunoassay
- MeSH terms
- Binding, Competitive, Breast Neoplasms, Female, Humans, Lymphatic Metastasis, Menopause, Radioimmunoassay, Receptors, Estrogen, Receptor, Insulin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review