Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions

M. H. Black, A. Magklara, C. Obiezu, M. A. Levesque, D. J A Sutherland, D. J. Tindall, C. Y F Young, E. R. Sauter, E. P. Diamandis

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The recent demonstration of human glandular kallikrein (hK2) expression in a breast carcinoma cell line has suggested that this putatively prostate-restricted, steroid hormone-regulated protease may also be expressed in breast epithelium in vivo and secreted into the mammary duct system. Given that the only substrate yet identified for hK2 activity is the precursor of prostate-specific antigen (PSA), the expression of which in breast carcinomas may be associated with favourable prognosis, our purpose was to examine the expression pattern of both hK2 and PSA in breast tumour tissues. Cytosolic extracts of 336 primary breast carcinomas prepared for routine oestrogen receptor (ER) and progesterone receptor (PR) analysis, as well as 31 nipple aspirates from six women with non-diseased mammary glands, were assayed for hK2 and PSA using immunofluorometric assays developed by the authors. In the tumour extracts, measurable hK2 and PSA concentrations were detected in 53% and 73% of cases respectively, and were positively correlated to each other (r = 0.59, P = 0.0001). Higher concentrations of PSA and hK2 were found in tumours expressing steroid hormone receptors (P = 0.0001 for PSA and P = 0.0001 for hK2, by Wilcoxon tests for both ER and PR), and both PSA (r = 0.25, P = 0.0001) and hK2 (r = 0.22, P = 0.0001) correlated directly with PR levels. A negative correlation between patient age and PSA (r = -0.12, P = 0.03) was also found. Both proteins were present in nipple aspirate fluid at relatively high concentrations which were positively correlated (r = 0.53, P = 0.002). The molecular weights of the immunoreactive species quantified by the hK2 and PSA assays were established by high-performance liquid chromatography (HPLC) and were consistent with the known molecular weights of hK2 and PSA. Together these data provide the first evidence, to our knowledge, that both malignant breast tissue and normal breast secretion contain measurable quantities of hK2, and that the degree of hK2 expression or secretion is directly proportional to the expression of PSA and steroid hormone receptors. hK2 expression may therefore be a marker of steroid hormone action in breast tissue.

Original languageEnglish (US)
Pages (from-to)361-367
Number of pages7
JournalBritish Journal of Cancer
Volume82
Issue number2
StatePublished - 2000

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Tissue Kallikreins
Prostate-Specific Antigen
Prostate
Breast
Breast Neoplasms
Proteins
Progesterone Receptors
Hormones
Steroid Receptors
Nipple Aspirate Fluid
Molecular Weight
Steroids
Fluoroimmunoassay
Nipples
Human Mammary Glands
Estrogen Receptors
Neoplasms
Peptide Hydrolases
Epithelium
High Pressure Liquid Chromatography

Keywords

  • Breast cancer
  • Human glandular kallikrein
  • Kallikrein gene family
  • Prostate cancer
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Black, M. H., Magklara, A., Obiezu, C., Levesque, M. A., Sutherland, D. J. A., Tindall, D. J., ... Diamandis, E. P. (2000). Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions. British Journal of Cancer, 82(2), 361-367.

Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions. / Black, M. H.; Magklara, A.; Obiezu, C.; Levesque, M. A.; Sutherland, D. J A; Tindall, D. J.; Young, C. Y F; Sauter, E. R.; Diamandis, E. P.

In: British Journal of Cancer, Vol. 82, No. 2, 2000, p. 361-367.

Research output: Contribution to journalArticle

Black, MH, Magklara, A, Obiezu, C, Levesque, MA, Sutherland, DJA, Tindall, DJ, Young, CYF, Sauter, ER & Diamandis, EP 2000, 'Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions', British Journal of Cancer, vol. 82, no. 2, pp. 361-367.
Black MH, Magklara A, Obiezu C, Levesque MA, Sutherland DJA, Tindall DJ et al. Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions. British Journal of Cancer. 2000;82(2):361-367.
Black, M. H. ; Magklara, A. ; Obiezu, C. ; Levesque, M. A. ; Sutherland, D. J A ; Tindall, D. J. ; Young, C. Y F ; Sauter, E. R. ; Diamandis, E. P. / Expression of a prostate associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions. In: British Journal of Cancer. 2000 ; Vol. 82, No. 2. pp. 361-367.
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