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.