Expression of sex steroid receptors and IGF-1 mRNA in breast tissue--effects of hormonal treatment.
The mechanisms behind increased breast tissue proliferation and a possibly increased breast cancer risk in women using hormonal contraception (HC) and hormonal replacement therapy (HRT) are incompletely understood. We analyzed breast tissue from 20 premenopausal and seven postmenopausal women undergoing reduction mammoplasties for estrogen receptor (ER) and progesterone receptor (PR) content as well as mRNA levels for ER, PR and insulin-like growth factor-1 (IGF-1). The receptor values were correlated to IGF-1 mRNA concentrations and levels of steroid and peptide hormones and SHBG. In women using HC, we found significantly lower ER values (p = 0.02) but non-significantly lower ER mRNA levels compared to those in naturally cycling women. PR and PR mRNA were no different. Women on HC displayed a higher breast tissue proliferation (p = 0.05) expressed as Ki-67, MIB-1 positivity, which was correlated with IGF-1 mRNA (r(s) = 0.82, p = 0.04). Since the concentration of sex steroid receptors in breast tissue is comparatively low and steroid receptors are down-regulated during hormonal treatment, mechanisms other than direct sex steroid receptor action are likely to be present. Our results suggest a role for IGF-1 in the proliferative response of breast tissue during exogenous hormonal treatment.
Isaksson
E
E
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. erika@rah.ks.se
Sahlin
L
L
Söderqvist
G
G
von Schoultz
E
E
Masironi
B
B
Wickman
M
M
Wilking
N
N
von Schoultz
B
B
Skoog
L
L
D000328:Adult; D000368:Aged; D001940:Breast / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D016462:Mammaplasty; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin