Prolactin as a local growth promoter in patients with breast cancer: GCRI experience

Jm, Bhatavdekar; Patel, Dev; Shah, Neelam G.; Hh, Vora; Suthar, Tejal P.; Ghosh, Nandita; Chikhlikar, PR; Trivedi, T.I.

doi:10.1053/ejso.2000.0943

Cited by 63 publications

(54 citation statements)

References 19 publications

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“…Alternatively, our results are consistent with the possibility that subclinical breast cancer may increase prolactin concentrations. Bhatavdekar et al (28) reported that immunohistochemical staining of prolactin in breast tumors was correlated with plasma prolactin concentrations (r ϭ 0.41). Thus, it is important for studies examining the relationship between prolactin and breast cancer to use a prospective design, especially in light of other evidence that prolactin secretion can be influenced by physical or psychological stress after diagnosis (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer

et al. 2004

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Prolactin is important in human breast development, and substantial laboratory and in vitro data suggest a role in mammary carcinogenesis. Therefore, we conducted a prospective case-control study nested within the Nurses' Health Study cohort to examine, in detail, the association between plasma prolactin concentrations and postmenopausal breast cancer by cancer invasiveness, estrogen receptor/progesterone receptor status, and other subject characteristics, including postmenopausal hormone use. Blood samples were collected from 1989 to 1990 and prolactin was measured by microparticle enzyme immunoassay. The analysis included 851 cases of postmenopausal breast cancer diagnosed after blood collection and before June 2000, in which there were one or two controls (n ‫؍‬ 1,275) matched on age, postmenopausal hormone use, fasting status, and time of day and month of blood collection. Prolactin was associated with a modestly increased risk of postmenopausal breast cancer [relative risk, top versus bottom quartile, 1.34; 95% confidence interval (CI), 1.02-1.76; P-trend ‫؍‬ 0.01]. The association differed by estrogen receptor/ progesterone receptor status (P-heterogeneity ‫؍‬ 0.03). The relative risk was 1.78 (95% CI, 1.28, 2.50; P-trend < 0.001) for estrogen receptor؉/ progesterone receptor؉, 0.76 (95% CI, 0.43, 1.32; P-trend ‫؍‬ 0.28) for estrogen receptor؊/progesterone receptor؊, and 1.94 (95% CI, 0.99, 3.78; P-trend ‫؍‬ 0.12) for estrogen receptor؉/progesterone receptor؊ breast cancers. Associations generally were similar for ductal and lobular carcinomas (P-heterogeneity ‫؍‬ 0.43) and by tumor size (P-heterogeneity ‫؍‬ 0.24). Among estrogen receptor؉/progesterone receptor؉ cancers, the association did not significantly differ by postmenopausal hormone use, years between blood draw and diagnosis, or after adjustment for estradiol (relative risk, 1.93; 95% CI, 1.16, 3.22; P-trend ‫؍‬ 0.01). Our prospective data suggest that plasma prolactin concentrations are associated with an increased risk of postmenopausal breast cancer, particularly for estrogen receptor؉/progesterone receptor؉ cancers, and independently of estradiol.

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Section: Discussionmentioning

confidence: 99%

Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer

et al. 2004

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“…Autocrine PRL is involved in the growth of breast cancer cells (Clevenger et al 1995, Ginsburg & Vonderhaar 1995 and several studies have linked a function of autocrine PRL to breast tumorigenesis (Touraine et al 1998, Vonderhaar 1999, Bhatavdekar et al 2000, Llovera et al 2000. High levels of serum PRL are associated with increased risk of breast cancer (Hankinson et al 1999), recurrence of metastatic breast cancer and reduced survival time (Bhatavdekar et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…High levels of serum PRL are associated with increased risk of breast cancer (Hankinson et al 1999), recurrence of metastatic breast cancer and reduced survival time (Bhatavdekar et al 2000). The hPRLR-SF1b is a strong dominant-negative to the differentiative function of the hPRLR-LF, leading us to hypothesize that it may regulate hPRLR-LF-mediated differentiation of breast epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…Serum PRL levels are also a recognized risk factor for recurrence and reduced survival time for both breast and colorectal cancer (Bhatavdekar et al 1992, Patel et al 1994. The effects of PRL may be realized through either the endocrine synthesis of PRL or its local autocrine/paracrine synthesis in various tissues including breast and colon cancer (Clevenger et al 1995, Ginsburg & Vonderhaar 1995, Touraine et al 1998, Bhatavdekar et al 2000, Llovera et al 2000. A recent report of a soluble PRL-binding protein present in human serum and milk derived from an as yet unidentified site(s) (Kline & Clevenger 2001) adds further complexity to the mechanism by which PRL probably acts on normal and neoplastic tissues.…”

Section: Introductionmentioning

confidence: 99%

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Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein

Trott

Hovey

Koduri

et al. 2003

Journal of Molecular Endocrinology

108

135

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Endocrine and autocrine prolactin (PRL) exerts effects on normal breast and breast cancer cells, and high serum PRL is a poor prognostic factor for colorectal cancer. Here we tested the hypothesis that short isoforms of the PRL receptor (PRLR) in human tissue regulate the actions of PRL in cancer. Using 3′ RACE we isolated five splice variants of the human PRLR (hPRLR), three of which encode the complete extracellular binding domain. Two of these isoforms, short form 1a (SF1a) and short form 1b (SF1b), possess unique intracellular domains encoded by splicing to exon 11 from exons 10 and 9 respectively. A third novel isoform (∆7/11) reflects alternative splicing from exon 7 to exon 11 and encodes a secreted soluble PRL-binding protein. Additional splice variants of SF1b and ∆7/11 that lacked exon 4 (∆4-SF1b and ∆4-∆7/11) were also identified. Functional analyses indicated that hPRLR-SF1b is a strong dominant-negative to the differentiative function of the PRLR long form while hPRLR-SF1a is a weaker dominant-negative. Differential abundance of SF1a, SF1b and ∆7/11 expression was detected in normal breast, colon, placenta, kidney, liver, ovary and pancreas, and breast and colon tumors. Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer.

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“…PRL is a peptide hormone primarily secreted by the pituitary gland, but extrapituitary synthesis by e.g. breast cancer cells has also been reported (Clevenger et al 1995, Ginsburg & Vonderhaar 1995, Bhatavdekar et al 2000. PRL acts through the PRL receptor (PRLR) belonging to the class I cytokine receptor family.…”

Section: Introductionmentioning

confidence: 99%

Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

Rasmussen¹,

Frederiksen²,

Din³

et al. 2010

Endocrine-Related Cancer

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The pituitary hormone prolactin (PRL) plays an important role in mammary gland development. It was also suggested to contribute to breast cancer progression. In vivo data strongly supported a crucial role of PRL in promoting tumour growth; however, PRL demonstrated only a weak, if any, pro-proliferative effect on cancer cells in vitro. Several recent studies indicated that PRL action in vivo may be influenced by the hormonal milieu, e.g. other growth factors such as 17b-oestradiol (E 2 ). Here, we explored the potential interplay between PRL and E 2 in regulation of gene expression and cell growth. PRL alone induced either a weak or no proliferative response of T47D and BT-483 cells respectively, while it drastically enhanced cell proliferation in E 2 -stimulated cultures. Affymetrix microarray analysis revealed 12 genes to be regulated by E 2 , while 57 genes were regulated by PRL in T47D cells. Most of the PRL-regulated genes (42/57) were not previously described as PRL target genes, e.g. WT1 and IER3. One hundred and five genes were found to be regulated upon PRL/E 2 co-treatment: highest up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3, SOCS3, WT1 and AREG. PRL and E 2 synergised to regulate EGR3, while multiple genes were regulated additively. These data show a novel interplay between PRL and E 2 to modulate gene regulation in breast cancer cells.

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Prolactin as a local growth promoter in patients with breast cancer: GCRI experience

Cited by 63 publications

References 19 publications

Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer

Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer

Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein

Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

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