Esther,
In the discussion, they do try to deal with the enigma of the protective
factor of lactation against breast cancer:
Both animal and in vitro models support the hypothesis that prolactin is
involved in mammary carcinogenesis. Several studies have reported that
breast cancer cells/tissue express prolactin (9
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B9#B9> ,
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B26#B26> 26,
27 <http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B27#B27> ,
28) <http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B28#B28>
and the prolactin receptor (8
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B8#B8> , 9
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B9#B9> , 10
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B10#B10> ,
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B28#B28> 28)
. Although normal tissue also expresses the prolactin receptor, primarily
along the luminal cell border, several studies have reported higher levels
in tumor tissue (10
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B10#B10> ,
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B29#B29> 29)
with expression primarily in the cytoplasm (8)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B8#B8> . In
mice, prolactin appears to induce tumor formation (30
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B30#B30> ,
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B31#B31> 31)
, increase tumor growth rate (5)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B5#B5> , and
increase the number of cells in the S phase (31)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B31#B31> .
In vitro studies also suggest that prolactin is associated with higher cell
proliferation rates (3
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B3#B3> , 4
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B4#B4> , 5)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B5#B5> ,
increases in cyclin D1 (3
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B3#B3> ,
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B4#B4> 4) ,
and it may induce motility of breast cancer cell lines (6)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B6#B6> .
Preliminary data also suggest that prolactin can enhance the responsiveness
of breast cancer cells to estradiol (3)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B3#B3> . In
humans, prolactin concentrations were positively associated with
mammographic density, a consistent strong breast cancer risk factor (32)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B32#B32> ,
among 189 postmenopausal women after adjustment for age and waist
circumference (33)
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B33#B33> .
Paradoxically, prolactin is temporarily increased during breastfeeding,
which is a protective factor for breast cancer. One possible explanation for
this discrepancy is that pregnancy is associated with a lifetime decrease in
prolactin levels
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B2#B2> (2) ,
and this may outweigh the transient prolactin increase during breastfeeding.
Secondly, the effect of prolactin during breastfeeding may differ from its
effect at other times in the reproductive life of a woman; for example, it
may lead to terminal cell differentiation during lactation but not at other
times.
From citation 2: In addition, the relationship between plasma and tissue PRL
levels is not well understood-further delineation of this relationship will
require work from both epidemiologists and laboratory scientists. Parous
women have been consistently observed to have lower PRL levels than
nulliparous women.
In vivo, of course, mammary function is regulated by complex interactions
among hormones, including PRL, estrogens, and progestins, as well as local
growth factors, such as EGF family members, IGFs, and TGF{alpha}, and the
different cell types present in the mammary tumor environment. These factors
can amplify or inhibit one another's signals to the epithelial cells by
several mechanisms, including altering expression of receptors, influencing
the level or activities of signaling pathways, and activating paracrine
modulators via action on different cell types (
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R118#R118> 118,
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R322#R322> 322,
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R323#R323> 323). These complex opportunities for
cross-talk are only beginning to be examined in these in vitro systems.
Recent findings emphasize the importance of understanding PRL actions in
cells of varying phenotype and environmental context.
Relatively little work has been done in nontumor human cell lines. The
murine mammary epithelial cell line, HC11, a clonal derivative of COMMA-D
cells, has been extensively studied. These cells proliferate in response to
growth factors. However, PRL, in combination with glucocorticoids, causes
these cells to grow more slowly, and differentiate, as characterized by milk
protein synthesis (
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R197#R197> 197,
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R324#R324> 324,
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R325#R325> 325,
<http://edrv.endojournals.org/cgi/content/full/24/1/1?ijkey=2403a331faad6c0b
94b9428622117c163fa73de8#R326#R326> 326). This is an especially important
area for study, which will increase our understanding of this hormone and
its interactions with other factors in normal and pathogenic processes.
From the article again:
This study has several limitations. First, several forms of prolactin
circulate in human plasma, which appear to have different biological
activities
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B45#B45> (45
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B46#B46> ,
46) . The immunoassay used in this study, which identify most prolactin
isoforms
<http://cancerres.aacrjournals.org/cgi/content/full/64/18/6814#B47#B47> (47)
, cannot distinguish between them. Therefore, we cannot isolate which
isoform or isoforms are most important in breast cancer development.
All in all, this was interesting and I gleaned some info. They note that
pregnancy (parity, from citation 2) is related to lower prolactin
concentrations later in life. But then they also acknowledge that the
immunoassay for prolactin receptor could not distinguish between types of
receptors, which could also play a huge role in how things can go wrong and
prolactin start feeding a cancer. Prolactin has a cross-over influence with
estrogen, which often does mediate cancer growth. The bottom line is that
there is more to the picture than just the finding of higher prolactin
levels among cancer patients. Lactation, generally speaking, does not pose
the risk; something going wrong with the normal phyisiology is the issue.
But you are right; someone reading this uncritically could jump to
conclusions.
Lisa
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