Lai, L. C.

Universiti Putra Malaysia Institutional Repository

UPM Research Report 1998: Volume 2IDENTIFICATION OF OESTRONE SULPHATASEINHIBITORS IN BREAST CYST FLUID: A NEWTREATMENT FOR BREAST CANCERi,c, LaiFaculty of Medicine and Health SciencesUniversiti Putra Malaysia, 43400 UPM, Serdang, Selangor, .MalaysiaKeywords: breast cancer, oestrone sulphatase, breastcyst fluid, oestrogens, growth factors.IntroductionOestrogens play an important role in the development ofbreast cancer. Oestrone sulphate is a major source of activeoestrogens in the breast, being converted to oestrone by oes-trone sulphatase. Oestrone is then converted to oestradiol, apotent oestrogen strongly implicated in the development ofbreast cancer, by the enzyme 1713-hydroxysteroiddehydro-genase. In vitro oestrone sulphatase activity in breast tissuehas been shown to be at least 1.000 times as high as aroma-tase activity, which converts androgens to oestrogens. Hence,local production of active oestrogens from oestrone sulphateis a very important source of oestrogens in breast tumours. Ihave previously found that breast cyst fluid is a potent in-hibitor of oestrone sulphatase activity in certain breast cancercell lines. Oestrone sulphatase inhibition is potentially ofgreat importance in the treatment of women with hormone-dependent breast cancers. The aim of this study was to iden-tify the substances present in breast cyst fluid which are re-sponsible for the oestrone sulphatase inhibitory property ofbreast cyst fluid.Materials and MethodsBreast cyst fluid was obtained by needle aspiration of palpa-ble breast cysts from women attending the Breast Clinic atUniversiti Hospital, Kuala Lumpur, under the care of Associ-ate Professor Dr. Yip Cheng Har. The samples were centri-fuged and the supernatant stored at -20°C until assayed.High performance liquid chromatography will be carried outto separate substances according to molecular weight andfractions which are found to inhibit oestrone sulphatase ac-316tivity in.breast cancer cell lines will be subjected to sodiumdodecyl sulphate-polyacrylamide gel electrophoresis. Elec-troblotting on to nitrocellulose were carried out and proteinsresponsible for oestrone sulphatase inhibition were identifiedby N-terrninal amino acid sequencing. The procedure forMCF-7 and MDA-MB-231 cell culture as well as the oes-trone sulphatase assay have been described (Erbas et al. 1996Results and DiscussionThis study is due to be completed at the end of the year 2000.Hence, the results described here are results, which havebeen obtained, in the first year of the study. Our preliminarystudies have shown that, unlike Western women where breastcyst fluid inhibits oestrone sulphatase activity in the MCF-7hormone-dependent breast cancer cell line and stimulatesoestrone sulphatase activity in the MBA-MD-23( hormone-independent breast cancer cell line, in our Malaysian popula-tion breast cyst fluid stimulates oestrone sulphatase activityin the MCF-7 cell line and inhibits oestrone sulphatase activ-ity in the MDA-MB-231 cell line. This difference betweenWestern and Malaysian females could be due the differencesin the proportions of the many constituents present in thebreast cyst fluid of the two female populations. The oestronesulphatase inhibitory property of breast cyst fluid is non-dialysable, using a dialysis membrane with a molecularweight cut-off of 3,500 daltons, implying that this propertyof breast cyst fluid is due to a high molecular weight sub-stance. The ability of breast cyst fluid to inhibit oestronesulphatase activity is retained after heat treatment for 60minutes at 65°C, implying that the substance(s) involved areheat stable. Work is now being conducted to identify thesubstances responsible for the oestrone sulphatase inhibitoryproperty of breast cyst fluid.ConclusionsThe oestrone sulphatase inhibitory property of breast cystfluid is due to one or more high molecular weight substances.ReferencesErbas, H., Lennard, T.W.J. and Lai, L.C. 1996. Effect of breast cystfluid on oestrone sulphatase activity in MCF-7 breast cancercells, Anticancer Research. 16: 833-836.Supported by [RPA Grant 06"()2-04-OO17

Identification of oestrone sulphatase inhibitors in breast cyst fluid: a new treatment for breast cancer

http://psasir.upm.edu.my/42995/1/Identification%20of%20oestrone%20sulphatase%20inhibitors%20in%20breast%20cyst%20fluid%20A%20new%20treatment%20for%20breast%20cancer.pdf

Identification of oestrone sulphatase inhibitors in breast cyst fluid: a new treatment for breast cancer

Abstract

Similar works

Full text

Available Versions

Universiti Putra Malaysia Institutional Repository