Nature article on HER2

[Soccermom]

http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng1963.html


http://www.nature.com/images/spacer.gifArticlehttp://www.nature.com/ng/images/spacer_grey.gifhttp://www.nature.com/images/spacer.gifPublished online: 28 January 2007; | doi:10.1038/ng1963 Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis

Sofi G Julien1, 5, Nadia Dubé1, 6, Michelle Read1, Janice Penney1, Marilene Paquet2, Yongxin Han3, Brian P Kennedy3, William J Muller4, 5 & Michel L Tremblay1, 5



Need some translation, if you could,Lani.

Thanks,Marcia

[Lani]

It implied that if mutation/deletion occurs in both the ECD(extracellular domain--the part of her2 outside the cell membrane) of her2 and in this PTP1B, then the formation of her2+ breast tumors and their metastasizing to the lung were both impeded (whereas just having the mutation of the ECD of her2 had the opposite effect).

These types of experiments are done ie, mutating or deleting gene 1 only vs gene 1 and 2 vs gene 2 only as a way of trying to dissect out what the function of genes are and how the proteins coded for by the genes are related and influence each other.

In this case mutating/deleting either her2ECD or PTP1B alone lead to tumor formation and/or metastasis whereas mutating/deleting both tended to prevent tumor formation and metastasis.

Obviously the full paper gave more of an explanation to their conclusion that the (down) regulation occcurs via inhibition of both the AKT and MAPK pathways that are downstream (occur after in a chronological fashion) of
her2.

This is basic science research trying to find out how all these genes and the proteins they code for interact, feedback on each other (either positively or negatively) in order to understand what drives a tumor and what inhibits it.

The hope is for deleting or inhibiting both ie, combining herceptin or another her2ECD inhibitor/complexing compound or antibody with another targetted treatment (antibody or small molecule) that targets PTP1B

Sounds very far from the lab bench into the clinic--but each little bit of understanding helps us understand the complex forces that drive tumors to divide and spread.

Hope this helps

[Soccermom]

Thanks Lani, Your explanation made sense of the study for me.
I will continue to post new articles asI come across them, if thats ok?

Praying for a cure with each abstract!

Marcia

[Lani]

There cannot be enough eyeballs perusing the literature, news reports, drug company announcements, etc. No matter how many hours a person spent
noone could spot them all.
That is why I particularly a couple of years ago listed which breast cancer cell lines (the cells they grow in perpetuity in petri dishes since they were taken from a patient's tumor years or decades ago) were her2+. All articles on breast cancer might be meaningful, but those specific to her2 are all the more relevant as it seems to be driven by different forces, behave in a different way and respond to different treatments or combinations of treatments.

[Lani]

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ErbB2 Inhibitor Delays Breast Cancer Growth, Protects Against Metastasis



NEW YORK (Reuters Health) Jan 31 - Deficiency or inhibition of protein tyrosine phosphatase 1B (PTP1B) increases breast tumor latency and inhibits lung metastasis, Canadian researchers report in a January 28th advance online publication of Nature Genetics.

Dr. Sofi G. Julien at McGill University in Montreal and colleagues are working on an anti-PTP1B treatment that they are testing in mouse models of ErbB2-induced breast cancers.

The ErbB2 oncogene, also known as Neu, it encodes a receptor tyrosine kinase (RTK) belonging to the epidermal growth factor receptor (EGFR), which is amplified in breast cancers. ErbB2 is found in approximately 25% of all breast cancers. A deletion in the Neu extracellular domain 2' (NDL2) leads to breast tumors with a high metastatic potential to the lung.

Dr. Julien and colleagues have found that deletion of PTP1B activity in the NDL2 transgenic mice, either by breeding or through treatment with a PTP1B inhibitor, resulted in "significant mammary tumor latency and resistance to lung metastasis." Overexpression of PTP1B resulted in spontaneous breast cancer development.

The researchers say that their findings have "therapeutic implications, and we propose that individuals with ErbB2-positive breast cancer might benefit from pharmacological inhibition of PTP1B activity in combination with anti-ErbB2 therapies."

Nat Gen 2007.