Leptin receptor expression and cell signalling in breast cancer--effecton MAPK, PI3K

Int J Oncol. 2006 Apr;28(4):985-93. Links

Leptin receptor expression and cell signaling in breast cancer.

Frankenberry KA, Skinner H, Somasundar P, McFadden DW, Vona-Davis LC.

Department of Surgery, West Virginia University, Morgantown, WV 26506, USA.

Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells. In addition, SOCS-3 expression (a leptin inducible inhibitor of leptin signaling), plus MAPK and PI3K signaling, were examined to determine their role in leptin-induced cell proliferation. Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin. Multiplex RT-PCR was performed to determine relative mRNA expression levels of the human short (huOB-Ra) or long (huOB-Rb) leptin receptor isoforms, or SOCS-3. MAPK and PI3K signaling was analyzed by phosphorylation of ERK and Akt, respectively, via Western blotting. Cell proliferation and inhibitor studies were analyzed by MTT assay. HTB-26 and ZR75-1 both expressed huOB-Ra, huOB-Rb and SOCS-3 mRNA; however, mRNA expression levels generally remained unchanged over time with leptin treatment. MAPK and PI3K pathways were activated in the presence of leptin over time. MAPK and PI3K inhibitors significantly blocked leptin-induced proliferation. Higher levels of circulating leptin contribute to breast cancer proliferation by activation of the MAPK and PI3K signaling pathways involved in cell growth and survival. The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS-3 mRNA expression.

PMID: 16525650 [PubMed - in process]

Interesting post as usual.

RB

[Bev]

I know this isn't science, but most patients I see at the oncs and at rad land are thin. Makes me feel bad, are we blaming the victim? BB

I am positive that these post are not trying to suggest blame.

The metabolism of the fats in the body is a hugely complex subject. I think what people are trying to do who read up on the subject is make sense of it all, and raise flags. It is often reported that there is a link between obesity and BC.

There are also reported links with fat balance omega threes and sixes and BC.

Exercise etc and intake restriction will lead to ordinary weight for some no matter what the balance of fat intake, or "quality of diet", others report it makes little difference.

Some will simply have a predisposition, or encountered some other factor.

Illness can lead to weight loss.

There is a body of thought that the increase in western diseases all inflamation linked may have strong links with low omega three and high six
and general quality of diet, which is where my posts are coming from.

Overall it is a huge very complex subject, with the unknowns just getting bigger as they find out more which is why there is so much debate on the subject.

RB