Endocrine Abstracts (2001) 2 P43

Variable expression of IGF-1 in breast cancer influences expression of c-myc and Cox-2

C Laban1, W Ogunkolade2, K Kirkpatrick1, S Bustin3, K Mokbel4, M Ghilichik5, R Carpenter1 & PJ Jenkins2


Depts of Breast Surgery1, Endocrinology2and Academic Surgery3St Bartholomew's and The Royal London; Dept of Breast Surgery, St Georges Hospital4and Dept of Pathology, Central Middlesex Hospital5, London


Background: IGF-1 is a ubiquitous growth factor that has been shown to play an important role in breast tissue development and tumorigenesis. Previously we have shown that IGF-1 expression is lost in approximately 1/3 of breast carcinomas. It is unsure whether this indicates the existence of a subset of breast cancers that may behave differently clinically and on a molecular level. Aims: To assess and quantify the mRNA expression of (i) Cox-2 and c-myc, genes implicated in breast tumourgenesis, and (ii) GH, GH receptor, IGF-1R and IGFBP-3, in the two groups (IGF-1 positive and IGF-1 negative) of breast carcinoma. Methods: Total RNA was extracted from samples of 32 breast cancers, of which 13 had absent IGF-1 expression. Using a real-time, hydrolysis probe dependent RT-PCR assay ('Taqman'), transcription was quantified and expressed as copy number/µg total RNA. Results: Expression of both c-myc and Cox-2 was significantly higher in the IGF-1 positive tumours. In addition the expression of GHR and IGFBP-3 was also increased in the IGF-1 positive breast cancer group. There was no difference in GH or IGF-1R expression between groups.

Median (range) log mRNA copy number/µg total RNA
c-mycCox-2GH-RIGFBP-3
IGF-1+ve
carcinoma
1.0E+08
(1.1E+09-
4.6E+07)
2.4E+06
(4.2E+07-
6.0E+05)
2.4E+07
(1.6E+09-
3.3E+05)
1.2E+07
(8.0E+07-
9.5E+05)
IGF-1-ve
carcinoma
5.7E+07*
(4.2E+08-
2.9E+06)
9.9E+05*
(2.4E+07-
8.9E+04)
2.9E+06*
(5.0E+07-
1.54E+02)
4.5E+06*
(7.6E+07-
2.24E+04)

Conclusions: There are two distinct groups of breast carcinoma, with respect to IGF-1 expression. The reduced expression of c-myc and cox-2 in the IGF-1 negative group suggests a lower level of proliferation and angiogenesis. However the clinical significance of these differences remains to be determined.

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