Immunocytochemical localization of insulin- and somatostatin-like material in human breast tumors

Stearns, Susan B.; Numann, Patricia J.; Smith, Phillip H.

doi:10.1016/0024-3205(84)90138-3

Cited by 12 publications

(5 citation statements)

References 24 publications

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“…Taken together, this is the first report on the intracellular presence of insulin and its phosphorylated, activated receptor in NSCLC tissue samples, thus adding to previous reports on the detection of insulin in human breast cancer specimens (Castro et al, 1980;Spring-Mills et al, 1984;.…”

Section: Journal Of Cellular Physiologysupporting

confidence: 65%

Intracellular presence of insulin and its phosphorylated receptor in non‐small cell lung cancer

Mattarocci¹,

Abbruzzese²,

Mileo³

et al. 2009

Journal Cellular Physiology

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Insulin has been known for a long time to influence the growth and differentiation of normal and transformed cells. In order to delineate the role of insulin specifically in non-small cell lung cancer (NSCLC), we have now searched by immunohistochemistry (IHC) for the presence of insulin in NSCLC samples. Among the 112 samples we studied, 30 were found to contain insulin, which was detected in the form of intracytoplasmic granula. Moreover, its expression significantly correlated with (a) the morphological/histopathological subtype of NSCLC, being more frequent in adenocarcinomas; (b) the grade of tumor differentiation, displaying an increase in low-grade carcinomas; (c) tumor size, occurring predominantly in smaller tumors; (d) the presence of phosphorylated, activated insulin receptor; (e) the median patient age, being present in relatively younger individuals. Furthermore and interestingly, surrounding atypical adenomatous hyperplastic areas and normal alveolar pneumocytes scored insulin-positive in some of the insulin-negative tumors. In addition, PCR exploration for insulin transcripts in some samples positive for immunoreactive insulin was negative, indicating a possibly exogenous origin for the intracellular insulin in our NSCLC cohort. Taken together, our data suggest that an intracellular insulin activity is important for the progression of low-grade human lung adenocarcinomas.

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Section: Journal Of Cellular Physiologysupporting

confidence: 65%

Intracellular presence of insulin and its phosphorylated receptor in non‐small cell lung cancer

Mattarocci¹,

Abbruzzese²,

Mileo³

et al. 2009

Journal Cellular Physiology

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“…Furthermore, we detected insulin protein in high-grade breast cancer employing an immunoassay, a result that is in line with early findings by other groups (Castro et al, 1980; Spring-Mills et al, 1984). …”

supporting

confidence: 92%

Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines

Weirich

Mengele

Yfanti

et al. 2008

BCHM

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Immunohistochemical evidence for ubiquitous distribution of metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, spleen) and on a cell microarray encompassing 31 tumor cell lines of different origin plus trophoblast cells, and normal blood lymphocytes and granulocytes. IDE protein is expressed by all of the tissues assessed and in all of the tumor cell lines except Raji and HL-60; trophoblast cells and granulocytes but not normal lymphocytes are also IDE-positive.

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“…Among these growth factors, insulin is of crucial importance. Insulin is able to promote the proliferation of human breast cancer cells (3,4) and has been demonstrated to be present in human mammary tumors (5), specifically either in the cytoplasmic or the nuclear compartment (6). Elevated blood levels of insulin have been shown to be associated with an adverse prognosis in early-stage breast cancer (7).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels

Radulescu¹,

Hufnagel²,

Luppa³

et al. 2007

Int J Oncol

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Insulin is a hormone crucial to metabolism and an essential growth factor for normal and neoplastic tissues. We have now determined insulin in extracts of 23 primary breast cancer specimens and of non-neoplastic breast tissues by a chemiluminescent immunoassay. Remarkably, insulin was measured only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland were each insulin-negative. We also performed immunohistochemistry for insulin-degrading enzyme (IDE), a cytoplasmic zinc metalloprotease belonging to the inverzincin family and participating in insulin cleavage. IDE was detected in most insulin-positive grade 3 carcinomas, indicating that it might be dysfunctional in these anaplastic tumors. IDE was equally present in the insulin-negative grade 2 carcinomas. Moreover, five grade 3 carcinomas and one grade 2 carcinoma displayed a loss of heterozygosity in the 10q chromosomal region harboring the IDE gene, but, despite these alterations, IDE was detected immunohistochemically, indicating a retention of the second allele. Compared to the expression of IDE in 92% of the tumors examined, only 57% of 21 normal breast specimens stained positively for IDE. In contrast to this increase in IDE-positive epithelial cells in breast cancer vs. normal breast, additional immunohistochemical analysis of 17 node-positive breast carcinomas and corresponding tumor-bearing lymph nodes showed that IDE expression decreases from primary tumor to lymph node metastasis. Altogether, this study represents the first demonstration of IDE in normal and neoplastic human mammary tissues. Our present report should also provide an experimental starting point towards exploring a potential role of IDE in the control of tumor progression.

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Immunocytochemical localization of insulin- and somatostatin-like material in human breast tumors

Cited by 12 publications

References 24 publications

Intracellular presence of insulin and its phosphorylated receptor in non‐small cell lung cancer

Intracellular presence of insulin and its phosphorylated receptor in non‐small cell lung cancer

Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines

Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels

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